(2R,6S)-tert-Butyl 2-(benzhydryl­carbamo­yl)-6-methyl­morpholine-4-carboxyl­ate

Wang, H.; Xia, G.; Liu, X.; Shen, J.

doi:10.1107/S1600536811017764

organic compounds

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ISSN: 2056-9890

Volume 67| Part 6| June 2011| Page o1437

doi:10.1107/S1600536811017764

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(2R,6S)-tert-Butyl 2-(benzhydrylcarbamoyl)-6-methylmorpholine-4-carboxylate

Haiyang Wang,^a Guangxin Xia,^b Xuejun Liu ^b and Jingkang Shen ^a ^*

^aShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China, and ^bCentral Research Institute, Shanghai Pharmaceutical Group Co. Ltd, 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China
^*Correspondence e-mail: xiagx@pharm-sh.com.cn

(Received 22 April 2011; accepted 11 May 2011; online 20 May 2011)

The title compound, C₂₄H₃₀N₂O₄, was obtained by the reaction of (2R,6S)-4-(tert-butoxycarbonyl)-6-methylmorpholine-2-carboxylic acid with diphenylmethanamine in dimethylformamide solution. The morpholine ring is in a chair conformation. In the crystal, weak intermolecular C—H⋯O hydrogen bonds link molecules into chains along the b axis.

Related literature

For a review of the biological relevance and synthesis of C-substituted morpholine derivatives, see: Wijtmans et al. (2004 ). For applications of morpholine derivatives as drugs, see: Dando & Perry (2004 ); Hajos et al. (2004 ); Hale et al. (1998 ); Versiani et al. (2002 ). For agrochemical fungicides and bactericides containing a morpholine skeleton, see: Dieckmann et al. (1993 ). For applications of morpholines as chiral auxiliaries in asymmetric synthesis, see: Dave & Sasaki (2004 ); Enders et al. (1994 ).

Experimental

Crystal data

C₂₄H₃₀N₂O₄
M_r = 410.50
Monoclinic, C 2
a = 27.248 (4) Å
b = 5.8241 (8) Å
c = 14.275 (2) Å
β = 94.192 (3)°
V = 2259.3 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 K
0.37 × 0.24 × 0.16 mm

Data collection

Bruker SMART APEX CCD diffractometer
5956 measured reflections
2310 independent reflections
1934 reflections with I > 2σ(I)
R_int = 0.110

Refinement

R[F² > 2σ(F²)] = 0.048
wR(F²) = 0.109
S = 0.96
2310 reflections
279 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C19—H19⋯O1ⁱ	0.93	2.54	3.332 (4)	144
Symmetry code: (i) x, y-1, z.

Data collection: SMART (Bruker, 2002 ); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811017764/cv5082sup1.cif

Supporting information file. DOI: 10.1107/S1600536811017764/cv5082Isup2.cdx

Structure factors: contains datablock I. DOI: 10.1107/S1600536811017764/cv5082Isup3.hkl

Supporting information file. DOI: 10.1107/S1600536811017764/cv5082Isup4.cml

checkCIF report

Comment top

Morpholines are an important class of heterocyclic compounds found in many naturally occurring or synthetically organic molecules (Wijtmans et al., 2004). Especially, the morpholine moiety has found widespread use in medicinal chemistry, and many drugs contain this subunit. For example, antidepressant drug Reboxetine (Hajos et al., 2004; Versiani et al., 2002), Aprepitant in combination with other agents to prevent and control nausea and vomiting caused by chemotherapy (Dando & Perry, 2004; Hale et al., 1998). The morpholine skeleton is also used to construct a number of agrochemical fungicides and bactericides, such as Fenpropimorph and tridemorph (Dieckmann et al., 1993). Furthermore, morpholines have been applied as chiral auxiliaries in asymmetric synthesis (Dave & Sasaki, 2004; Enders et al., 1994). Herewith we report the crystal structure of the title compound (I).

In (I) (Fig. 1), the morpholine ring is in a chair conformation. Weak intermolecular C—H···O hydrogen bonds (Table 1) link the molecules related by translation along axis b into chains.

Related literature top

For a review of the biological relevance and synthesis of C-substituted morpholine derivatives, see: Wijtmans et al. (2004). For applications of morpholine derivatives as drugs, see: Dando & Perry (2004); Hajos et al. (2004); Hale et al. (1998); Versiani et al. (2002). For agrochemical fungicides and bactericides containing a morpholine skeleton, see: Dieckmann et al. (1993). For applications of morpholines as chiral auxiliaries in asymmetric synthesis, see: Dave & Sasaki (2004); Enders et al. (1994).

Experimental top

The schematic representation of the synthesis is given in Fig. 2. To a solution of EDC (125 mg, 0.54 mmol) and HOAt (74 mg, 0.54 mmol) in DMF (2 ml) was added diphenylmethanamine (82 mg, 0.45 mmol) and (2R,6S)-4-(tert-butoxycarbonyl)-6-methylmorpholine-2-carboxylic acid (132 mg, 0.54 mmol) and the mixture stirred at room temperature overnight. The mixture was then partitioned between EtOAc and water. The organic layer was then washed successively with saturated aqueous sodium bicarbonate, brine and then dried (MgSO4). The solution was evaporated to dryness in vacuo and the residue purified by flash column chromatography to give the title compound (124 mg) as a colourless solid. Crystals suitable for X-ray structure analysis were obtained by slow evaporation of a solution in EtOAc at room temperature.

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. View of (I) showing the atomic numbering. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Schematic representation of the synthesis.

(2R,6S)-tert-Butyl 2-[(diphenylmethyl)carbamoyl]-6-methylmorpholine-4-carboxylate top

Crystal data top

C₂₄H₃₀N₂O₄	F(000) = 880
M_r = 410.50	D_x = 1.207 Mg m⁻³
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 2344 reflections
a = 27.248 (4) Å	θ = 5.7–47.9°
b = 5.8241 (8) Å	µ = 0.08 mm⁻¹
c = 14.275 (2) Å	T = 293 K
β = 94.192 (3)°	Prismatic, white
V = 2259.3 (5) Å³	0.37 × 0.24 × 0.16 mm
Z = 4

Data collection top

Bruker SMART APEX CCD diffractometer	1934 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.110
Graphite monochromator	θ_max = 25.5°, θ_min = 2.0°
ϕ and ω scans	h = −32→27
5956 measured reflections	k = −6→7
2310 independent reflections	l = −17→16

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.109	H atoms treated by a mixture of independent and constrained refinement
S = 0.96	w = 1/[σ²(F_o²) + (0.0542P)²] where P = (F_o² + 2F_c²)/3
2310 reflections	(Δ/σ)_max = 0.018
279 parameters	Δρ_max = 0.15 e Å⁻³
1 restraint	Δρ_min = −0.23 e Å⁻³

Crystal data top

C₂₄H₃₀N₂O₄	V = 2259.3 (5) Å³
M_r = 410.50	Z = 4
Monoclinic, C2	Mo Kα radiation
a = 27.248 (4) Å	µ = 0.08 mm⁻¹
b = 5.8241 (8) Å	T = 293 K
c = 14.275 (2) Å	0.37 × 0.24 × 0.16 mm
β = 94.192 (3)°

Data collection top

Bruker SMART APEX CCD diffractometer	1934 reflections with I > 2σ(I)
5956 measured reflections	R_int = 0.110
2310 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.048	1 restraint
wR(F²) = 0.109	H atoms treated by a mixture of independent and constrained refinement
S = 0.96	Δρ_max = 0.15 e Å⁻³
2310 reflections	Δρ_min = −0.23 e Å⁻³
279 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.38365 (9)	0.0550 (5)	−0.09403 (17)	0.0726 (8)
N2	0.32924 (10)	0.1668 (4)	0.19729 (14)	0.0582 (7)
O1	0.36972 (10)	0.4751 (5)	0.15139 (14)	0.0892 (8)
O2	0.30774 (6)	0.0299 (3)	0.02574 (11)	0.0516 (5)
O3	0.39908 (8)	0.0609 (4)	−0.24661 (13)	0.0740 (6)
O4	0.43729 (7)	0.3050 (4)	−0.14171 (13)	0.0649 (6)
C1	0.34746 (10)	0.2991 (5)	0.13400 (17)	0.0504 (6)
C2	0.34143 (9)	0.2148 (5)	0.03370 (16)	0.0484 (6)
H2	0.3284	0.3407	−0.0063	0.058*
C3	0.39051 (10)	0.1440 (7)	0.00143 (19)	0.0702 (9)
H3A	0.4125	0.2750	0.0031	0.084*
H3B	0.4051	0.0268	0.0429	0.084*
C4	0.34907 (11)	−0.1318 (6)	−0.1033 (2)	0.0677 (8)
H4A	0.3621	−0.2628	−0.0677	0.081*
H4B	0.3443	−0.1769	−0.1687	0.081*
C5	0.30039 (10)	−0.0621 (5)	−0.06807 (17)	0.0529 (7)
H5	0.2804	−0.2014	−0.0645	0.064*
C6	0.27212 (12)	0.1025 (7)	−0.13283 (19)	0.0747 (9)
H6A	0.2429	0.1509	−0.1047	0.112*
H6B	0.2632	0.0278	−0.1916	0.112*
H6C	0.2922	0.2339	−0.1435	0.112*
C7	0.33164 (10)	0.2209 (5)	0.29757 (15)	0.0528 (7)
H7	0.3432	0.3797	0.3048	0.063*
C8	0.28101 (10)	0.2103 (5)	0.33392 (16)	0.0512 (6)
C9	0.25146 (10)	0.0219 (6)	0.31751 (19)	0.0610 (7)
H9	0.2632	−0.1026	0.2850	0.073*
C10	0.20460 (11)	0.0133 (7)	0.3483 (2)	0.0739 (9)
H10	0.1847	−0.1143	0.3353	0.089*
C11	0.18741 (13)	0.1950 (8)	0.3985 (2)	0.0795 (10)
H11	0.1558	0.1915	0.4192	0.095*
C12	0.21685 (14)	0.3780 (8)	0.4174 (2)	0.0825 (11)
H12	0.2056	0.4985	0.4529	0.099*
C13	0.26342 (13)	0.3900 (6)	0.38514 (18)	0.0684 (8)
H13	0.2829	0.5189	0.3979	0.082*
C14	0.36812 (9)	0.0700 (5)	0.35412 (16)	0.0486 (6)
C15	0.38313 (10)	0.1338 (6)	0.44504 (18)	0.0625 (8)
H15	0.3716	0.2702	0.4692	0.075*
C16	0.41486 (12)	−0.0017 (8)	0.5002 (2)	0.0775 (10)
H16	0.4245	0.0440	0.5612	0.093*
C17	0.43244 (11)	−0.2042 (8)	0.4660 (3)	0.0787 (10)
H17	0.4539	−0.2958	0.5033	0.094*
C18	0.41775 (11)	−0.2685 (7)	0.3760 (2)	0.0744 (9)
H18	0.4293	−0.4051	0.3521	0.089*
C19	0.38604 (11)	−0.1329 (6)	0.32084 (19)	0.0606 (7)
H19	0.3765	−0.1792	0.2599	0.073*
C20	0.40627 (10)	0.1365 (5)	−0.16836 (19)	0.0562 (7)
C21	0.47203 (10)	0.3996 (5)	−0.20592 (19)	0.0570 (7)
C22	0.49962 (12)	0.5747 (6)	−0.1450 (2)	0.0765 (9)
H22A	0.4769	0.6863	−0.1239	0.115*
H22B	0.5235	0.6500	−0.1805	0.115*
H22C	0.5160	0.4996	−0.0916	0.115*
C23	0.50568 (12)	0.2101 (6)	−0.2339 (3)	0.0787 (10)
H23A	0.5194	0.1329	−0.1786	0.118*
H23B	0.5317	0.2743	−0.2674	0.118*
H23C	0.4873	0.1025	−0.2735	0.118*
C24	0.44503 (13)	0.5127 (7)	−0.2886 (2)	0.0795 (9)
H24A	0.4274	0.3987	−0.3262	0.119*
H24B	0.4681	0.5892	−0.3256	0.119*
H24C	0.4222	0.6228	−0.2670	0.119*
H2A	0.3113 (11)	0.060 (6)	0.181 (2)	0.058 (9)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0724 (14)	0.096 (2)	0.0528 (13)	−0.0328 (16)	0.0287 (11)	−0.0251 (14)
N2	0.0865 (17)	0.0596 (16)	0.0294 (10)	−0.0232 (15)	0.0104 (10)	−0.0025 (11)
O1	0.1344 (19)	0.0868 (17)	0.0501 (11)	−0.0546 (17)	0.0324 (12)	−0.0172 (11)
O2	0.0594 (10)	0.0633 (12)	0.0333 (8)	−0.0150 (10)	0.0120 (7)	0.0012 (8)
O3	0.0932 (14)	0.0820 (16)	0.0498 (11)	−0.0177 (13)	0.0264 (10)	−0.0213 (11)
O4	0.0692 (11)	0.0794 (14)	0.0489 (10)	−0.0184 (12)	0.0226 (9)	−0.0078 (10)
C1	0.0606 (15)	0.0540 (16)	0.0374 (13)	−0.0084 (14)	0.0102 (11)	0.0000 (12)
C2	0.0617 (14)	0.0529 (15)	0.0318 (12)	−0.0124 (13)	0.0101 (10)	0.0041 (12)
C3	0.0651 (16)	0.104 (3)	0.0432 (14)	−0.0235 (18)	0.0182 (12)	−0.0143 (16)
C4	0.0791 (19)	0.066 (2)	0.0606 (17)	−0.0091 (17)	0.0238 (14)	−0.0143 (16)
C5	0.0658 (15)	0.0556 (17)	0.0388 (13)	−0.0199 (14)	0.0129 (11)	−0.0045 (12)
C6	0.086 (2)	0.091 (2)	0.0453 (15)	−0.010 (2)	−0.0075 (14)	−0.0075 (17)
C7	0.0807 (17)	0.0498 (15)	0.0284 (11)	−0.0124 (14)	0.0080 (11)	−0.0035 (12)
C8	0.0711 (16)	0.0536 (16)	0.0291 (11)	0.0047 (14)	0.0055 (11)	0.0035 (12)
C9	0.0695 (17)	0.0628 (19)	0.0515 (15)	0.0025 (17)	0.0093 (13)	−0.0056 (14)
C10	0.0677 (18)	0.091 (2)	0.0636 (18)	0.000 (2)	0.0090 (15)	0.0064 (19)
C11	0.073 (2)	0.104 (3)	0.0630 (19)	0.024 (2)	0.0158 (16)	0.008 (2)
C12	0.104 (3)	0.088 (3)	0.0577 (18)	0.035 (2)	0.0246 (17)	−0.002 (2)
C13	0.102 (2)	0.0628 (19)	0.0417 (14)	0.0082 (19)	0.0094 (15)	−0.0034 (15)
C14	0.0553 (13)	0.0569 (17)	0.0355 (12)	−0.0131 (13)	0.0173 (10)	−0.0044 (12)
C15	0.0768 (18)	0.072 (2)	0.0391 (13)	−0.0027 (17)	0.0048 (13)	−0.0101 (14)
C16	0.079 (2)	0.101 (3)	0.0518 (17)	−0.007 (2)	−0.0050 (15)	−0.0046 (19)
C17	0.0581 (17)	0.105 (3)	0.074 (2)	0.007 (2)	0.0088 (15)	0.018 (2)
C18	0.0694 (18)	0.078 (2)	0.079 (2)	0.0090 (18)	0.0257 (16)	0.0008 (19)
C19	0.0711 (17)	0.0677 (19)	0.0446 (14)	−0.0044 (16)	0.0152 (12)	−0.0072 (15)
C20	0.0553 (14)	0.0636 (17)	0.0517 (16)	−0.0059 (14)	0.0183 (12)	−0.0122 (14)
C21	0.0616 (16)	0.0558 (16)	0.0564 (15)	0.0001 (14)	0.0221 (12)	0.0089 (14)
C22	0.0780 (19)	0.074 (2)	0.079 (2)	−0.0112 (19)	0.0170 (16)	0.0076 (19)
C23	0.0762 (19)	0.067 (2)	0.097 (3)	0.0062 (19)	0.0353 (17)	0.007 (2)
C24	0.102 (2)	0.071 (2)	0.0663 (19)	0.007 (2)	0.0086 (17)	0.0084 (17)

Geometric parameters (Å, º) top

N1—C20	1.352 (4)	C9—H9	0.9300
N1—C4	1.439 (4)	C10—C11	1.379 (5)
N1—C3	1.457 (3)	C10—H10	0.9300
N2—C1	1.312 (3)	C11—C12	1.349 (6)
N2—C7	1.463 (3)	C11—H11	0.9300
N2—H2A	0.81 (3)	C12—C13	1.383 (5)
O1—C1	1.207 (4)	C12—H12	0.9300
O2—C2	1.414 (3)	C13—H13	0.9300
O2—C5	1.443 (3)	C14—C19	1.376 (4)
O3—C20	1.203 (3)	C14—C15	1.383 (3)
O4—C20	1.332 (3)	C15—C16	1.375 (5)
O4—C21	1.472 (3)	C15—H15	0.9300
C1—C2	1.511 (3)	C16—C17	1.376 (6)
C2—C3	1.503 (4)	C16—H16	0.9300
C2—H2	0.9800	C17—C18	1.369 (5)
C3—H3A	0.9700	C17—H17	0.9300
C3—H3B	0.9700	C18—C19	1.376 (4)
C4—C5	1.508 (4)	C18—H18	0.9300
C4—H4A	0.9700	C19—H19	0.9300
C4—H4B	0.9700	C21—C24	1.497 (4)
C5—C6	1.504 (4)	C21—C22	1.505 (5)
C5—H5	0.9800	C21—C23	1.507 (4)
C6—H6A	0.9600	C22—H22A	0.9600
C6—H6B	0.9600	C22—H22B	0.9600
C6—H6C	0.9600	C22—H22C	0.9600
C7—C8	1.510 (4)	C23—H23A	0.9600
C7—C14	1.515 (4)	C23—H23B	0.9600
C7—H7	0.9800	C23—H23C	0.9600
C8—C9	1.371 (4)	C24—H24A	0.9600
C8—C13	1.382 (4)	C24—H24B	0.9600
C9—C10	1.382 (4)	C24—H24C	0.9600

C20—N1—C4	121.8 (2)	C9—C10—H10	120.2
C20—N1—C3	125.1 (3)	C12—C11—C10	119.4 (3)
C4—N1—C3	113.2 (2)	C12—C11—H11	120.3
C1—N2—C7	123.7 (2)	C10—C11—H11	120.3
C1—N2—H2A	120 (2)	C11—C12—C13	121.3 (3)
C7—N2—H2A	115 (2)	C11—C12—H12	119.4
C2—O2—C5	113.74 (17)	C13—C12—H12	119.4
C20—O4—C21	121.4 (2)	C8—C13—C12	120.0 (4)
O1—C1—N2	124.5 (2)	C8—C13—H13	120.0
O1—C1—C2	119.3 (2)	C12—C13—H13	120.0
N2—C1—C2	116.1 (2)	C19—C14—C15	117.8 (3)
O2—C2—C3	110.7 (2)	C19—C14—C7	123.3 (2)
O2—C2—C1	110.40 (19)	C15—C14—C7	118.8 (2)
C3—C2—C1	110.0 (2)	C16—C15—C14	120.9 (3)
O2—C2—H2	108.6	C16—C15—H15	119.6
C3—C2—H2	108.6	C14—C15—H15	119.6
C1—C2—H2	108.6	C15—C16—C17	120.6 (3)
N1—C3—C2	109.1 (2)	C15—C16—H16	119.7
N1—C3—H3A	109.9	C17—C16—H16	119.7
C2—C3—H3A	109.9	C18—C17—C16	118.8 (3)
N1—C3—H3B	109.9	C18—C17—H17	120.6
C2—C3—H3B	109.9	C16—C17—H17	120.6
H3A—C3—H3B	108.3	C17—C18—C19	120.6 (3)
N1—C4—C5	110.6 (3)	C17—C18—H18	119.7
N1—C4—H4A	109.5	C19—C18—H18	119.7
C5—C4—H4A	109.5	C18—C19—C14	121.3 (3)
N1—C4—H4B	109.5	C18—C19—H19	119.4
C5—C4—H4B	109.5	C14—C19—H19	119.4
H4A—C4—H4B	108.1	O3—C20—O4	126.3 (3)
O2—C5—C6	111.3 (2)	O3—C20—N1	123.2 (3)
O2—C5—C4	110.1 (2)	O4—C20—N1	110.5 (2)
C6—C5—C4	112.9 (2)	O4—C21—C24	110.7 (2)
O2—C5—H5	107.4	O4—C21—C22	102.1 (2)
C6—C5—H5	107.4	C24—C21—C22	110.7 (3)
C4—C5—H5	107.4	O4—C21—C23	108.8 (2)
C5—C6—H6A	109.5	C24—C21—C23	112.8 (3)
C5—C6—H6B	109.5	C22—C21—C23	111.2 (3)
H6A—C6—H6B	109.5	C21—C22—H22A	109.5
C5—C6—H6C	109.5	C21—C22—H22B	109.5
H6A—C6—H6C	109.5	H22A—C22—H22B	109.5
H6B—C6—H6C	109.5	C21—C22—H22C	109.5
N2—C7—C8	110.5 (2)	H22A—C22—H22C	109.5
N2—C7—C14	112.2 (2)	H22B—C22—H22C	109.5
C8—C7—C14	111.9 (2)	C21—C23—H23A	109.5
N2—C7—H7	107.3	C21—C23—H23B	109.5
C8—C7—H7	107.3	H23A—C23—H23B	109.5
C14—C7—H7	107.3	C21—C23—H23C	109.5
C9—C8—C13	118.3 (3)	H23A—C23—H23C	109.5
C9—C8—C7	120.9 (2)	H23B—C23—H23C	109.5
C13—C8—C7	120.8 (3)	C21—C24—H24A	109.5
C8—C9—C10	121.3 (3)	C21—C24—H24B	109.5
C8—C9—H9	119.4	H24A—C24—H24B	109.5
C10—C9—H9	119.4	C21—C24—H24C	109.5
C11—C10—C9	119.6 (4)	H24A—C24—H24C	109.5
C11—C10—H10	120.2	H24B—C24—H24C	109.5

C7—N2—C1—O1	2.9 (5)	C9—C10—C11—C12	−0.5 (5)
C7—N2—C1—C2	−180.0 (2)	C10—C11—C12—C13	1.9 (5)
C5—O2—C2—C3	−57.3 (3)	C9—C8—C13—C12	−0.8 (4)
C5—O2—C2—C1	−179.4 (2)	C7—C8—C13—C12	179.6 (2)
O1—C1—C2—O2	−170.2 (3)	C11—C12—C13—C8	−1.3 (5)
N2—C1—C2—O2	12.4 (3)	N2—C7—C14—C19	−17.3 (3)
O1—C1—C2—C3	67.3 (4)	C8—C7—C14—C19	107.6 (3)
N2—C1—C2—C3	−110.0 (3)	N2—C7—C14—C15	165.0 (2)
C20—N1—C3—C2	123.2 (3)	C8—C7—C14—C15	−70.1 (3)
C4—N1—C3—C2	−56.1 (4)	C19—C14—C15—C16	−0.1 (4)
O2—C2—C3—N1	55.5 (3)	C7—C14—C15—C16	177.8 (3)
C1—C2—C3—N1	177.8 (3)	C14—C15—C16—C17	0.0 (5)
C20—N1—C4—C5	−124.0 (3)	C15—C16—C17—C18	0.0 (5)
C3—N1—C4—C5	55.3 (4)	C16—C17—C18—C19	0.1 (5)
C2—O2—C5—C6	−70.7 (3)	C17—C18—C19—C14	−0.2 (4)
C2—O2—C5—C4	55.4 (3)	C15—C14—C19—C18	0.1 (4)
N1—C4—C5—O2	−52.7 (3)	C7—C14—C19—C18	−177.6 (3)
N1—C4—C5—C6	72.4 (3)	C21—O4—C20—O3	−8.3 (4)
C1—N2—C7—C8	126.8 (3)	C21—O4—C20—N1	170.6 (3)
C1—N2—C7—C14	−107.5 (3)	C4—N1—C20—O3	0.4 (5)
N2—C7—C8—C9	51.2 (3)	C3—N1—C20—O3	−178.8 (3)
C14—C7—C8—C9	−74.6 (3)	C4—N1—C20—O4	−178.5 (3)
N2—C7—C8—C13	−129.2 (3)	C3—N1—C20—O4	2.3 (4)
C14—C7—C8—C13	105.0 (3)	C20—O4—C21—C24	63.9 (4)
C13—C8—C9—C10	2.1 (4)	C20—O4—C21—C22	−178.2 (2)
C7—C8—C9—C10	−178.2 (2)	C20—O4—C21—C23	−60.5 (3)
C8—C9—C10—C11	−1.5 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C19—H19···O1ⁱ	0.93	2.54	3.332 (4)	144

Symmetry code: (i) x, y−1, z.

Experimental details

Crystal data
Chemical formula	C₂₄H₃₀N₂O₄
M_r	410.50
Crystal system, space group	Monoclinic, C2
Temperature (K)	293
a, b, c (Å)	27.248 (4), 5.8241 (8), 14.275 (2)
β (°)	94.192 (3)
V (Å³)	2259.3 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.37 × 0.24 × 0.16

Data collection
Diffractometer	Bruker SMART APEX CCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	5956, 2310, 1934
R_int	0.110
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.048, 0.109, 0.96
No. of reflections	2310
No. of parameters	279
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.15, −0.23

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C19—H19···O1ⁱ	0.93	2.54	3.332 (4)	144

Symmetry code: (i) x, y−1, z.

Acknowledgements

HW is indebted to Professor Jianshu Xie for supporting this project and for critical review of the manuscript. We gratefully acknowledge financial support from the Shanghai Pharmaceutical Group Co. Ltd GX is grateful to the Shanghai Postdoctoral Sustentation Fund, China (grant No. 07R214213) for financial support.

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