Di-tert-butyl N-[2,6-bis­(methoxy­meth­oxy)phen­yl]imino­diacetate

Capuano, B.; Crosby, I.T.; Forsyth, C.M.; Khakham, Y.; Manallack, D.T.

doi:10.1107/S1600536809009246

organic compounds

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ISSN: 2056-9890

Volume 65| Part 4| April 2009| Page o819

doi:10.1107/S1600536809009246

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Di-tert-butyl N-[2,6-bis(methoxymethoxy)phenyl]iminodiacetate

Ben Capuano,^a Ian T. Crosby,^a Craig M. Forsyth,^b ^* Yelena Khakham ^a and David T. Manallack ^a

^aMedicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Park Parade, Parkville, Victoria 3052, Australia, and ^bSchool of Chemistry, Monash University, Clayton, Victoria 3800, Australia
^*Correspondence e-mail: craig.forsyth@sci.monash.edu.au

(Received 4 March 2009; accepted 13 March 2009; online 25 March 2009)

The title molecule, C₂₀H₃₁NO₈, has pseudo-C2 symmetry about the C—N bond, with the bis(tert-butoxycarbonyl)amino group twisted from the benzene ring plane by ca 60° and the bulky tert-butoxycarbonyl (Boc) groups are orientated away from the substituted aniline group. As part of an antibacterial drug discovery programme furnishing analogues of platensimycin, we unexpectedly synthesized the bis-Boc-protected aniline.

Related literature

For the synthesis, see: Nicolaou et al. (2006 )Khakham (2007 ). For related structures, see: Marino et al. (2002 ); Macleod et al. (2003 ). For the protection of amino groups in synthesis, see: ; Kshirsagar (2008 ).

Experimental

Crystal data

C₂₀H₃₁NO₈
M_r = 413.46
Monoclinic, P 2₁ /c
a = 11.2544 (3) Å
b = 19.6759 (6) Å
c = 9.8325 (3) Å
β = 93.207 (1)°
V = 2173.90 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 123 K
0.25 × 0.25 × 0.25 mm

Data collection

Bruker X8 APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1997 ) T_min = 0.95, T_max = 0.97
15504 measured reflections
4207 independent reflections
3714 reflections with I > 2σ(I)
R_int = 0.026

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.095
S = 1.05
4207 reflections
264 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ); cell refinement: APEX2 and SAINT (Bruker, 2005); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001 ); software used to prepare material for publication: CIFTAB (Sheldrick, 1997).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809009246/pv2145sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809009246/pv2145Isup2.hkl

checkCIF report

Comment top

Protection of amino functionalities utilizing bulky tert-butylcarboxy groups is a common synthetic strategy in drug dicovery research programmes (Kshirsagar, 2008). Typically, mono-substituted derivatives are formed from reactions of anilines and di-tert-butyldicarbonate, with di-substitution generally inhibited by the poorer nucleophilic character of the intermediate secondary carbamate. In the current example, reaction of 2,6-bis(methoxymethoxy)aniline with the di-tert-butyldicarbonate gave 2-[bis(tert-butoxycarbonyl)amino]-1,3-bis(methoxymethoxy)benzene (I) in good yield. Surprisingly NMR spectra showed no evidence of restricted rotation of the tert-butoxycarbonyl groups in solution. The solid state structure showed a pseudo C2 symmetric molecule with the two methoxymethoxy arms of the benzene nucleus forming an S-shaped configuration. The bis(tert-butoxycarbonyl)amino fragment is twisted from the aromatic ring plane with the torsion angles C2—C1—N1—C12 57.7 (2) °; C6—C1—N1—C11 59.7 (2) ° smaller than for an analogous bis Boc aniline di-tert-butyl(2-(2-((4-methylphenyl)thio)-5-oxo-3-(3-oxohexyl) tetrahydrofuran-3-yl)phenyl)imidocarbonate (II) (73.6 °, 93.3 °) Marino et al. 2002), but larger than those observed for mono-protected anilines (e.g. 36.3 (3) ° in 2-(2'-N-tert-butoxycarbonyl)phenyl-1,3-dithiane (Macleod et al. 2003). The bulky tert-butoxycarbonyl groups are orientated away from the aniline group in I and II in contrast to the only other bis(tert-butoxycarbonyl)aniline structure, 2-(2'(N,N'-bis(tert-butoxycarbonyl)amino)phenyl-1,3-dithiane, in which the carbonyl groups point away from the aromatic ring (Macleod et al. 2003). No significant interactions between molecules of the title compound were observed (closest contact O7···H7a(#1) 2.474 Å, #1 x, 1/2 - y, 1/2 + z) and the observed configuration presumably derives from the steric repulsion between the ortho methoxymethoxy substitutents of the analine and the bulky tert-butoxycarbonyl groups.

Related literature top

For background literature, see: Nicolaou et al. (2006). For related structures, see: Marino et al. (2002); Macleod et al. (2003).

For related literature, see: Khakham (2007); Kshirsagar (2008).

Experimental top

The title compound (I) was synthesized from 2,6-bis(methoxymethoxy)aniline (Nicolaou et al., 2006) and commercially available di-tert-butyldicarbonate in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP), using tetrahydrofuran as solvent (Khakham, 2007). To a 50 ml round bottom flask was added 2,6-di(methoxymethoxy)aniline (0.820 g, 3.85 mmol) and di-tert-butyldicarbonate (2.51 g, 11.5 mmol) and 4-(dimethylamino)pyridine (0.120 g, 0.982 mmol) and tetrahydrofuran (15 ml). The reaction mixture was heated at reflux with stirring for 24 h, cooled then evaporated to dryness. The resulting residue was purified by flash chromatography (1:4 ethyl acetate/hexane) and the major fractions were combined then evaporated to dryness. The title compound was recrystallized from dichloromethane-hexane as colorless needles (549 mg, 46%) suitable for X-ray diffraction. Mp 366–367 K.

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2 (Bruker, 2005); data reduction: APEX2 (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: CIFTAB (Sheldrick, 1997).

Figures top

Fig. 1. Molecular diagram of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

Di-tert-butyl N-[2,6-bis(methoxymethoxy)phenyl]iminodiacetate top

Crystal data top

C₂₀H₃₁NO₈	F(000) = 888
M_r = 413.46	D_x = 1.263 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 15504 reflections
a = 11.2544 (3) Å	θ = 2.1–26.0°
b = 19.6759 (6) Å	µ = 0.10 mm⁻¹
c = 9.8325 (3) Å	T = 123 K
β = 93.207 (1)°	Prism, colourless
V = 2173.90 (11) Å³	0.25 × 0.25 × 0.25 mm
Z = 4

Data collection top

Bruker X8 APEX CCD diffractometer	4207 independent reflections
Radiation source: fine-focus sealed tube	3714 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.026
Thin–slice ϕ and ω scans	θ_max = 26.0°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1997)	h = −13→11
T_min = 0.95, T_max = 0.97	k = −24→24
15504 measured reflections	l = −12→12

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.095	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0455P)² + 0.7413P] where P = (F_o² + 2F_c²)/3
4207 reflections	(Δ/σ)_max < 0.001
264 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₂₀H₃₁NO₈	V = 2173.90 (11) Å³
M_r = 413.46	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.2544 (3) Å	µ = 0.10 mm⁻¹
b = 19.6759 (6) Å	T = 123 K
c = 9.8325 (3) Å	0.25 × 0.25 × 0.25 mm
β = 93.207 (1)°

Data collection top

Bruker X8 APEX CCD diffractometer	4207 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1997)	3714 reflections with I > 2σ(I)
T_min = 0.95, T_max = 0.97	R_int = 0.026
15504 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.095	H-atom parameters constrained
S = 1.05	Δρ_max = 0.25 e Å⁻³
4207 reflections	Δρ_min = −0.22 e Å⁻³
264 parameters

Special details top

Experimental. ¹H NMR (CDCl₃) δ 1.45(18H, s, tert-Bu), 3.51 (6H, s, OCH₃), 5.21 (4H, s, OCH₂O), 6.85 (2H, d, J = 8 Hz, H3 H5), 7.21 (1H, t, J = 8 Hz, H4). ¹³C NMR (CDCl₃) δ 27.9 (CH₃), 56.0 (CH₃), 82.0 (CH₂), 95.0 (CH₂), 108.7 (CH), 128.7 (CH), 151.5 (C_q), 162.0 (C_q). ESI MS (20 V) m/z 844 ([2M+NH₄]⁺, 25%), 414 ([M+H]⁺, 26%), 358 (35%), 302 (100%), 258 (40%), 182 (39%).

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
O1	0.01820 (8)	0.15220 (4)	0.49516 (9)	0.0208 (2)
O2	−0.17789 (8)	0.19162 (5)	0.45496 (10)	0.0239 (2)
O3	0.20418 (8)	0.02812 (4)	0.84955 (9)	0.0222 (2)
O4	0.22082 (9)	−0.08991 (5)	0.87902 (10)	0.0275 (2)
O5	0.32175 (8)	0.04924 (4)	0.57699 (9)	0.0226 (2)
O6	0.40454 (8)	0.13528 (5)	0.70366 (9)	0.0215 (2)
O7	0.10556 (8)	0.22153 (4)	0.75269 (9)	0.0209 (2)
O8	0.26357 (8)	0.23752 (4)	0.62311 (9)	0.0189 (2)
N1	0.20550 (9)	0.13091 (5)	0.66923 (10)	0.0170 (2)
C1	0.10389 (11)	0.08748 (6)	0.67245 (12)	0.0169 (3)
C2	0.00578 (11)	0.09870 (6)	0.58212 (12)	0.0183 (3)
C3	−0.09338 (12)	0.05666 (6)	0.58451 (14)	0.0224 (3)
H3	−0.1612	0.0646	0.5247	0.027*
C4	−0.09125 (12)	0.00289 (7)	0.67605 (14)	0.0245 (3)
H4	−0.1581	−0.0266	0.6766	0.029*
C5	0.00498 (12)	−0.00910 (6)	0.76637 (14)	0.0228 (3)
H5	0.0042	−0.0461	0.8283	0.027*
C6	0.10309 (11)	0.03395 (6)	0.76507 (12)	0.0188 (3)
C7	−0.07663 (12)	0.16675 (7)	0.39715 (13)	0.0223 (3)
H7A	−0.0489	0.2006	0.3315	0.027*
H7B	−0.0976	0.1247	0.3459	0.027*
C8	−0.15998 (14)	0.25694 (7)	0.51580 (17)	0.0344 (4)
H8A	−0.1033	0.2531	0.5948	0.052*
H8B	−0.2360	0.2744	0.5452	0.052*
H8C	−0.1284	0.2882	0.4492	0.052*
C9	0.21192 (14)	−0.02718 (7)	0.94256 (13)	0.0283 (3)
H9A	0.2824	−0.0206	1.0061	0.034*
H9B	0.1405	−0.0271	0.9969	0.034*
C10	0.32667 (13)	−0.09618 (8)	0.80655 (16)	0.0331 (3)
H10A	0.3254	−0.0626	0.7328	0.050*
H10B	0.3310	−0.1420	0.7681	0.050*
H10C	0.3962	−0.0882	0.8690	0.050*
C11	0.31523 (11)	0.10078 (6)	0.64174 (12)	0.0174 (3)
C12	0.18617 (11)	0.20088 (6)	0.68888 (11)	0.0159 (2)
C13	0.52977 (12)	0.11794 (7)	0.67929 (14)	0.0246 (3)
C14	0.55807 (14)	0.04678 (8)	0.73059 (17)	0.0376 (4)
H14A	0.5129	0.0136	0.6741	0.056*
H14B	0.5362	0.0427	0.8253	0.056*
H14C	0.6434	0.0380	0.7255	0.056*
C15	0.59817 (13)	0.17074 (9)	0.76495 (17)	0.0393 (4)
H15A	0.5830	0.1640	0.8612	0.059*
H15B	0.5721	0.2163	0.7365	0.059*
H15C	0.6835	0.1659	0.7524	0.059*
C16	0.55154 (13)	0.12683 (9)	0.53009 (15)	0.0351 (4)
H16A	0.5067	0.0923	0.4767	0.053*
H16B	0.6367	0.1217	0.5165	0.053*
H16C	0.5253	0.1722	0.5003	0.053*
C17	0.26643 (12)	0.31241 (6)	0.63900 (13)	0.0200 (3)
C18	0.15042 (12)	0.34337 (7)	0.58381 (13)	0.0238 (3)
H18A	0.1360	0.3304	0.4881	0.036*
H18B	0.1551	0.3930	0.5910	0.036*
H18C	0.0851	0.3267	0.6366	0.036*
C19	0.36707 (13)	0.33176 (7)	0.54976 (16)	0.0295 (3)
H19A	0.3453	0.3197	0.4549	0.044*
H19B	0.4395	0.3073	0.5804	0.044*
H19C	0.3813	0.3808	0.5563	0.044*
C20	0.29631 (14)	0.33007 (7)	0.78745 (14)	0.0310 (3)
H20A	0.3721	0.3088	0.8174	0.047*
H20B	0.2332	0.3133	0.8434	0.047*
H20C	0.3029	0.3795	0.7973	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0161 (5)	0.0216 (5)	0.0245 (5)	−0.0008 (4)	−0.0005 (4)	0.0046 (4)
O2	0.0167 (5)	0.0224 (5)	0.0325 (5)	0.0018 (4)	0.0003 (4)	−0.0031 (4)
O3	0.0259 (5)	0.0183 (5)	0.0222 (4)	0.0018 (4)	−0.0017 (4)	0.0016 (3)
O4	0.0336 (6)	0.0189 (5)	0.0300 (5)	0.0040 (4)	0.0022 (4)	0.0032 (4)
O5	0.0207 (5)	0.0203 (5)	0.0269 (5)	0.0022 (4)	0.0023 (4)	−0.0058 (4)
O6	0.0128 (5)	0.0250 (5)	0.0265 (5)	0.0006 (4)	−0.0003 (4)	−0.0060 (4)
O7	0.0225 (5)	0.0181 (4)	0.0227 (4)	0.0014 (4)	0.0074 (4)	−0.0008 (3)
O8	0.0200 (5)	0.0143 (4)	0.0227 (4)	−0.0020 (3)	0.0056 (4)	−0.0010 (3)
N1	0.0135 (5)	0.0146 (5)	0.0230 (5)	0.0002 (4)	0.0017 (4)	−0.0006 (4)
C1	0.0150 (6)	0.0138 (6)	0.0222 (6)	−0.0001 (5)	0.0047 (5)	−0.0026 (5)
C2	0.0176 (7)	0.0157 (6)	0.0219 (6)	0.0022 (5)	0.0050 (5)	−0.0013 (5)
C3	0.0150 (7)	0.0208 (6)	0.0314 (7)	0.0007 (5)	0.0024 (5)	−0.0028 (5)
C4	0.0177 (7)	0.0174 (6)	0.0394 (8)	−0.0031 (5)	0.0102 (6)	−0.0032 (5)
C5	0.0251 (7)	0.0142 (6)	0.0302 (7)	0.0006 (5)	0.0114 (6)	0.0019 (5)
C6	0.0203 (7)	0.0159 (6)	0.0205 (6)	0.0038 (5)	0.0042 (5)	−0.0032 (5)
C7	0.0195 (7)	0.0260 (7)	0.0210 (6)	0.0024 (5)	−0.0016 (5)	−0.0002 (5)
C8	0.0310 (9)	0.0256 (7)	0.0462 (9)	0.0045 (6)	−0.0015 (7)	−0.0094 (6)
C9	0.0428 (9)	0.0222 (7)	0.0197 (6)	0.0051 (6)	0.0017 (6)	0.0033 (5)
C10	0.0296 (8)	0.0281 (8)	0.0415 (8)	0.0070 (6)	0.0001 (6)	−0.0030 (6)
C11	0.0158 (7)	0.0188 (6)	0.0175 (6)	0.0001 (5)	0.0020 (5)	0.0025 (5)
C12	0.0170 (6)	0.0156 (6)	0.0149 (5)	−0.0004 (5)	−0.0011 (5)	−0.0001 (4)
C13	0.0123 (7)	0.0344 (8)	0.0269 (7)	0.0022 (5)	0.0004 (5)	−0.0017 (6)
C14	0.0230 (8)	0.0432 (9)	0.0461 (9)	0.0101 (7)	−0.0037 (7)	0.0073 (7)
C15	0.0194 (8)	0.0537 (10)	0.0445 (9)	−0.0062 (7)	−0.0029 (7)	−0.0104 (8)
C16	0.0192 (8)	0.0569 (10)	0.0295 (8)	−0.0030 (7)	0.0037 (6)	0.0026 (7)
C17	0.0243 (7)	0.0125 (6)	0.0235 (6)	−0.0036 (5)	0.0021 (5)	−0.0007 (5)
C18	0.0275 (8)	0.0195 (6)	0.0249 (6)	0.0018 (5)	0.0046 (5)	0.0037 (5)
C19	0.0261 (8)	0.0219 (7)	0.0413 (8)	−0.0044 (6)	0.0085 (6)	0.0039 (6)
C20	0.0412 (9)	0.0235 (7)	0.0275 (7)	−0.0060 (6)	−0.0066 (6)	−0.0038 (6)

Geometric parameters (Å, º) top

O1—C2	1.3683 (15)	C8—H8C	0.9800
O1—C7	1.4264 (15)	C9—H9A	0.9900
O2—C7	1.3907 (16)	C9—H9B	0.9900
O2—C8	1.4272 (16)	C10—H10A	0.9800
O3—C6	1.3754 (16)	C10—H10B	0.9800
O3—C9	1.4210 (15)	C10—H10C	0.9800
O4—C9	1.3894 (16)	C13—C16	1.5109 (19)
O4—C10	1.4272 (18)	C13—C14	1.516 (2)
O5—C11	1.2017 (15)	C13—C15	1.519 (2)
O6—C11	1.3317 (15)	C14—H14A	0.9800
O6—C13	1.4825 (16)	C14—H14B	0.9800
O7—C12	1.2023 (15)	C14—H14C	0.9800
O8—C12	1.3266 (15)	C15—H15A	0.9800
O8—C17	1.4820 (14)	C15—H15B	0.9800
N1—C12	1.4088 (15)	C15—H15C	0.9800
N1—C11	1.4096 (16)	C16—H16A	0.9800
N1—C1	1.4292 (16)	C16—H16B	0.9800
C1—C6	1.3928 (17)	C16—H16C	0.9800
C1—C2	1.3954 (18)	C17—C18	1.5136 (19)
C2—C3	1.3903 (18)	C17—C19	1.5195 (18)
C3—C4	1.3884 (19)	C17—C20	1.5196 (18)
C3—H3	0.9500	C18—H18A	0.9800
C4—C5	1.382 (2)	C18—H18B	0.9800
C4—H4	0.9500	C18—H18C	0.9800
C5—C6	1.3923 (18)	C19—H19A	0.9800
C5—H5	0.9500	C19—H19B	0.9800
C7—H7A	0.9900	C19—H19C	0.9800
C7—H7B	0.9900	C20—H20A	0.9800
C8—H8A	0.9800	C20—H20B	0.9800
C8—H8B	0.9800	C20—H20C	0.9800

C2—O1—C7	118.55 (10)	O6—C11—N1	110.18 (10)
C7—O2—C8	112.86 (11)	O7—C12—O8	127.29 (11)
C6—O3—C9	118.13 (10)	O7—C12—N1	121.92 (11)
C9—O4—C10	112.61 (11)	O8—C12—N1	110.71 (10)
C11—O6—C13	120.59 (10)	O6—C13—C16	109.73 (11)
C12—O8—C17	120.00 (9)	O6—C13—C14	110.04 (11)
C12—N1—C11	125.51 (10)	C16—C13—C14	112.79 (13)
C12—N1—C1	116.83 (10)	O6—C13—C15	102.12 (11)
C11—N1—C1	117.61 (10)	C16—C13—C15	110.76 (13)
C6—C1—C2	120.13 (11)	C14—C13—C15	110.89 (13)
C6—C1—N1	120.07 (11)	C13—C14—H14A	109.5
C2—C1—N1	119.80 (11)	C13—C14—H14B	109.5
O1—C2—C3	125.34 (12)	H14A—C14—H14B	109.5
O1—C2—C1	114.49 (11)	C13—C14—H14C	109.5
C3—C2—C1	120.17 (12)	H14A—C14—H14C	109.5
C4—C3—C2	118.65 (12)	H14B—C14—H14C	109.5
C4—C3—H3	120.7	C13—C15—H15A	109.5
C2—C3—H3	120.7	C13—C15—H15B	109.5
C5—C4—C3	122.09 (12)	H15A—C15—H15B	109.5
C5—C4—H4	119.0	C13—C15—H15C	109.5
C3—C4—H4	119.0	H15A—C15—H15C	109.5
C4—C5—C6	118.93 (12)	H15B—C15—H15C	109.5
C4—C5—H5	120.5	C13—C16—H16A	109.5
C6—C5—H5	120.5	C13—C16—H16B	109.5
O3—C6—C5	124.99 (11)	H16A—C16—H16B	109.5
O3—C6—C1	115.00 (11)	C13—C16—H16C	109.5
C5—C6—C1	120.01 (12)	H16A—C16—H16C	109.5
O2—C7—O1	113.19 (10)	H16B—C16—H16C	109.5
O2—C7—H7A	108.9	O8—C17—C18	110.43 (10)
O1—C7—H7A	108.9	O8—C17—C19	101.58 (10)
O2—C7—H7B	108.9	C18—C17—C19	110.37 (11)
O1—C7—H7B	108.9	O8—C17—C20	109.33 (10)
H7A—C7—H7B	107.8	C18—C17—C20	113.10 (11)
O2—C8—H8A	109.5	C19—C17—C20	111.43 (12)
O2—C8—H8B	109.5	C17—C18—H18A	109.5
H8A—C8—H8B	109.5	C17—C18—H18B	109.5
O2—C8—H8C	109.5	H18A—C18—H18B	109.5
H8A—C8—H8C	109.5	C17—C18—H18C	109.5
H8B—C8—H8C	109.5	H18A—C18—H18C	109.5
O4—C9—O3	113.22 (10)	H18B—C18—H18C	109.5
O4—C9—H9A	108.9	C17—C19—H19A	109.5
O3—C9—H9A	108.9	C17—C19—H19B	109.5
O4—C9—H9B	108.9	H19A—C19—H19B	109.5
O3—C9—H9B	108.9	C17—C19—H19C	109.5
H9A—C9—H9B	107.7	H19A—C19—H19C	109.5
O4—C10—H10A	109.5	H19B—C19—H19C	109.5
O4—C10—H10B	109.5	C17—C20—H20A	109.5
H10A—C10—H10B	109.5	C17—C20—H20B	109.5
O4—C10—H10C	109.5	H20A—C20—H20B	109.5
H10A—C10—H10C	109.5	C17—C20—H20C	109.5
H10B—C10—H10C	109.5	H20A—C20—H20C	109.5
O5—C11—O6	127.26 (12)	H20B—C20—H20C	109.5
O5—C11—N1	122.45 (11)

C2—C1—N1—C12	57.65 (15)	C6—C1—N1—C11	59.68 (15)

Experimental details

Crystal data
Chemical formula	C₂₀H₃₁NO₈
M_r	413.46
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	123
a, b, c (Å)	11.2544 (3), 19.6759 (6), 9.8325 (3)
β (°)	93.207 (1)
V (Å³)	2173.90 (11)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.25 × 0.25 × 0.25

Data collection
Diffractometer	Bruker X8 APEX CCD diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1997)
T_min, T_max	0.95, 0.97
No. of measured, independent and observed [I > 2σ(I)] reflections	15504, 4207, 3714
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.095, 1.05
No. of reflections	4207
No. of parameters	264
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.22

Computer programs: APEX2 (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), X-SEED (Barbour, 2001), CIFTAB (Sheldrick, 1997).

Acknowledgements

The authors acknowledge support from Monash University and the Australian Research Council.

References

Barbour, L. J. (2001). J. Supramol. Chem. 1, 189–191. CrossRef CAS Google Scholar
Bruker (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Khakham, Y. (2007). Honours thesis, Monash University (Parkville), Victoria, Australia. Google Scholar
Kshirsagar, T. (2008). High-Throughput Lead Optimization in Drug Discovery. Boca Raton: CRC Press. Google Scholar
Macleod, C., McKiernan, G. J., Guthrie, E. J., Farrugia, L. J., Hamprecht, D. W., Macritchie, J. & Hartley, R. C. (2003). J. Org. Chem. 68, 387–401. Web of Science CSD CrossRef PubMed CAS Google Scholar
Marino, J. P., Rubio, M. B., Cao, G. & de Dios, A. (2002). J. Am. Chem. Soc. 124, 13398–13399. Web of Science CSD CrossRef PubMed CAS Google Scholar
Nicolaou, K. C., Li, A. & Edmonds, D. J. (2006). Angew. Chem. Int. Ed. 45, 7086–7090. Web of Science CrossRef CAS Google Scholar
Sheldrick, G. M. (1997). SADABS and CIFTAB. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar