Ethyl 12b-allyl-1-hydr­oxy-3,6,7,12b-tetra­hydro-4H-1,3-dioxolo[4,5-g]pyrido[2,1-a]isoquinoline-2-carboxyl­ate

The title compound, C₂₀H₂₃NO₅, is an advanced inter­mediate used in the total synthesis of cephalotaxine. An intra­molecular O—H...O hydrogen bond exists in the crystal structure.

Key indicators

• Single-crystal X-ray study
• T = 294 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.084
• wR factor = 0.180
• Data-to-parameter ratio = 14.1

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT031_ALERT_4_B Refined Extinction Parameter within Range ......       2.44 Sigma
PLAT220_ALERT_2_B Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       4.06 Ratio
PLAT368_ALERT_2_B Short  C(sp2)-C(sp2) Bond  C16    -   C17    ...       1.09 Ang.

Alert level C
DIFMX01_ALERT_2_C  The maximum difference density is > 0.1*ZMAX*0.75
            _refine_diff_density_max given =      0.601
            Test value =      0.600
DIFMX02_ALERT_1_C  The maximum difference density is > 0.1*ZMAX*0.75
            The relevant atom site should be identified.
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT222_ALERT_3_C Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       3.94 Ratio
PLAT230_ALERT_2_C Hirshfeld Test Diff for    C16    -   C17     ..       6.23 su
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for         O2
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for         C8
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C15
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          6

   0 ALERT level A = In general: serious problem
   3 ALERT level B = Potentially serious problem
   9 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   7 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

Computing details

Data collection: SMART (Bruker, 2000); cell refinement: SMART; data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2000); software used to prepare material for publication: SHELXTL.

Ethyl 12b-allyl-1-hydroxy-3,6,7,12b-tetrahydro-4H-1,3-dioxolo[4,5-g]pyrido[2,1-a]isoquinoline-2-carboxylate

Crystal data

C20H23NO5	F(000) = 760
Mr = 357.39	Dx = 1.321 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.5365 (7) Å	Cell parameters from 1800 reflections
b = 20.0523 (18) Å	θ = 2.2–26.8°
c = 10.6574 (9) Å	µ = 0.10 mm^−1
β = 99.854 (4)°	T = 294 K
V = 1797.4 (3) Å^3	Plate, colorless
Z = 4	0.29 × 0.13 × 0.06 mm

Data collection

Bruker SMART CCD area-detector diffractometer	1915 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.054
Graphite monochromator	θmax = 25.5°, θmin = 2.0°
φ and ω scans	h = −10→9
9495 measured reflections	k = −24→19
3350 independent reflections	l = −12→12

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.084	H-atom parameters constrained
wR(F^2) = 0.180	w = 1/[σ^2(Fo^2) + (0.0336P)^2 + 2.3489P] where P = (Fo^2 + 2Fc^2)/3
S = 1.16	(Δ/σ)max < 0.001
3350 reflections	Δρmax = 0.60 e Å^−3
238 parameters	Δρmin = −0.40 e Å^−3
6 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0022 (9)

Special details

Experimental. IR (film): 3430, 2909, 1740, 1650, 1483, 1225, 1039 cm^-1; ¹H NMR (300 MHz, CDCl₃): δ 1.30 (t, J = 7.0 Hz, 3H), 2.18–3.06 (m, 9H), 3.30–3.40 (m, 1H), 4.18–4.26 (m, 2H), 4.99–5.09 (m, 2H), 5.63–5.78 (m, 1H), 5.87 (s, 1H), 5.89 (s, 1H), 6.52 (s, 1H), 7.46 (s, 1H), 13.04 (s, 1H, –OH); ¹³C NMR (75 MHz, CDCl₃): δ 14.1, 21.7, 24.2, 43.4, 44.7, 45.0, 60.5, 63.8, 97.4, 100.6, 108.1, 108.5, 116.3, 126.7, 130.5, 134.1, 145.8, 146.0, 171.7, 172.9

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O5	0.3644 (3)	0.72684 (13)	0.6686 (3)	0.0517 (8)
H5	0.4297	0.7171	0.6235	0.078*
N1	0.0345 (4)	0.62860 (15)	0.7403 (3)	0.0423 (8)
O3	0.4766 (4)	0.66506 (14)	0.4938 (3)	0.0602 (9)
O4	0.3496 (4)	0.57247 (14)	0.4151 (3)	0.0600 (9)
O2	−0.2179 (4)	0.93117 (15)	0.6902 (4)	0.0810 (11)
O1	0.0411 (4)	0.93451 (13)	0.6546 (3)	0.0616 (9)
C4	0.0957 (5)	0.81455 (18)	0.6949 (4)	0.0399 (10)
H4	0.2013	0.8170	0.6840	0.048*
C14	0.1324 (5)	0.68983 (18)	0.7464 (4)	0.0387 (10)
C3	0.0006 (5)	0.86979 (19)	0.6826 (4)	0.0452 (10)
C5	0.0280 (5)	0.75370 (18)	0.7247 (4)	0.0409 (10)
C13	0.2449 (4)	0.68203 (18)	0.6510 (4)	0.0396 (10)
C18	0.3633 (5)	0.6268 (2)	0.4889 (4)	0.0484 (11)
C15	0.2356 (5)	0.6956 (2)	0.8804 (4)	0.0506 (11)
H15A	0.3038	0.7344	0.8817	0.061*
H15B	0.1661	0.7031	0.9421	0.061*
C12	0.2358 (5)	0.63344 (19)	0.5618 (4)	0.0434 (10)
C10	−0.0322 (5)	0.6102 (2)	0.6089 (4)	0.0513 (11)
H10A	−0.0831	0.6486	0.5641	0.062*
H10B	−0.1118	0.5756	0.6089	0.062*
C9	−0.0881 (5)	0.6339 (2)	0.8199 (4)	0.0561 (12)
H9A	−0.0376	0.6424	0.9071	0.067*
H9B	−0.1436	0.5916	0.8184	0.067*
C2	−0.1523 (5)	0.8677 (2)	0.7027 (5)	0.0561 (12)
C8	−0.2074 (6)	0.6883 (2)	0.7777 (6)	0.0746 (16)
H8A	−0.2677	0.6973	0.8452	0.090*
H8B	−0.2813	0.6733	0.7036	0.090*
C7	−0.2206 (5)	0.8102 (2)	0.7342 (5)	0.0692 (15)
H7	−0.3252	0.8095	0.7480	0.083*
C11	0.0984 (5)	0.5853 (2)	0.5430 (4)	0.0523 (12)
H11A	0.0582	0.5802	0.4527	0.063*
H11B	0.1343	0.5420	0.5769	0.063*
C1	−0.1059 (6)	0.9698 (2)	0.6392 (5)	0.0648 (14)
H1A	−0.0909	1.0123	0.6828	0.078*
H1B	−0.1440	0.9782	0.5495	0.078*
C6	−0.1276 (5)	0.7521 (2)	0.7451 (4)	0.0541 (12)
C20	0.4405 (7)	0.4979 (3)	0.2711 (5)	0.0840 (18)
H20A	0.4252	0.4631	0.3296	0.126*
H20B	0.5274	0.4865	0.2287	0.126*
H20C	0.3455	0.5033	0.2093	0.126*
C19	0.4770 (6)	0.5614 (2)	0.3421 (5)	0.0728 (15)
H19A	0.5786	0.5582	0.3988	0.087*
H19B	0.4819	0.5980	0.2834	0.087*
C16	0.3354 (8)	0.6371 (3)	0.9202 (6)	0.102 (2)
H16	0.2845	0.5978	0.8904	0.122*
C17	0.4534 (11)	0.6274 (4)	0.9753 (7)	0.157 (3)
H17A	0.5168	0.6627	1.0105	0.189*
H17B	0.4903	0.5838	0.9871	0.189*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O5	0.0412 (18)	0.0425 (16)	0.074 (2)	−0.0055 (14)	0.0182 (15)	−0.0062 (15)
N1	0.047 (2)	0.0362 (18)	0.045 (2)	−0.0063 (16)	0.0097 (17)	0.0009 (15)
O3	0.052 (2)	0.0479 (18)	0.086 (2)	−0.0039 (15)	0.0265 (17)	−0.0056 (16)
O4	0.065 (2)	0.0515 (19)	0.070 (2)	−0.0038 (16)	0.0281 (17)	−0.0143 (16)
O2	0.065 (2)	0.0422 (19)	0.138 (3)	0.0138 (17)	0.025 (2)	0.002 (2)
O1	0.062 (2)	0.0333 (16)	0.091 (2)	0.0017 (15)	0.0182 (18)	0.0075 (16)
C4	0.036 (2)	0.038 (2)	0.047 (2)	−0.0026 (18)	0.0137 (19)	−0.0014 (19)
C14	0.045 (2)	0.029 (2)	0.041 (2)	−0.0013 (17)	0.0045 (19)	0.0008 (17)
C3	0.057 (3)	0.031 (2)	0.049 (2)	0.000 (2)	0.011 (2)	−0.0018 (19)
C5	0.048 (3)	0.036 (2)	0.040 (2)	−0.0004 (19)	0.0115 (19)	−0.0009 (18)
C13	0.030 (2)	0.035 (2)	0.055 (2)	0.0032 (18)	0.0095 (19)	0.0079 (19)
C18	0.048 (3)	0.041 (2)	0.057 (3)	0.005 (2)	0.012 (2)	0.002 (2)
C15	0.060 (3)	0.041 (2)	0.048 (3)	−0.004 (2)	0.001 (2)	0.002 (2)
C12	0.046 (3)	0.036 (2)	0.048 (2)	−0.0003 (19)	0.008 (2)	−0.0015 (19)
C10	0.049 (3)	0.050 (3)	0.055 (3)	−0.010 (2)	0.008 (2)	−0.004 (2)
C9	0.066 (3)	0.041 (2)	0.065 (3)	−0.012 (2)	0.023 (3)	0.002 (2)
C2	0.049 (3)	0.038 (2)	0.083 (3)	0.009 (2)	0.017 (3)	−0.002 (2)
C8	0.063 (3)	0.050 (3)	0.122 (5)	−0.005 (3)	0.047 (3)	0.006 (3)
C7	0.041 (3)	0.053 (3)	0.121 (4)	0.003 (2)	0.032 (3)	−0.004 (3)
C11	0.054 (3)	0.051 (3)	0.052 (3)	−0.010 (2)	0.010 (2)	−0.008 (2)
C1	0.080 (4)	0.041 (3)	0.076 (3)	0.013 (3)	0.022 (3)	−0.001 (2)
C6	0.049 (3)	0.043 (2)	0.076 (3)	0.001 (2)	0.027 (2)	−0.001 (2)
C20	0.089 (4)	0.072 (4)	0.100 (4)	−0.001 (3)	0.043 (4)	−0.025 (3)
C19	0.073 (4)	0.069 (3)	0.085 (4)	−0.006 (3)	0.040 (3)	−0.020 (3)
C16	0.121 (5)	0.052 (3)	0.101 (5)	0.012 (3)	−0.069 (4)	−0.010 (3)
C17	0.167 (7)	0.175 (7)	0.112 (5)	0.091 (6)	−0.025 (5)	−0.046 (5)

Geometric parameters (Å, º)

O5—C13	1.348 (4)	C10—C11	1.501 (6)
O5—H5	0.8200	C10—H10A	0.9700
N1—C9	1.459 (5)	C10—H10B	0.9700
N1—C10	1.466 (5)	C9—C8	1.509 (6)
N1—C14	1.480 (5)	C9—H9A	0.9700
O3—C18	1.229 (5)	C9—H9B	0.9700
O4—C18	1.338 (5)	C2—C7	1.359 (6)
O4—C19	1.458 (5)	C8—C6	1.517 (6)
O2—C2	1.387 (5)	C8—H8A	0.9700
O2—C1	1.410 (5)	C8—H8B	0.9700
O1—C3	1.389 (4)	C7—C6	1.405 (6)
O1—C1	1.425 (5)	C7—H7	0.9300
C4—C3	1.366 (5)	C11—H11A	0.9700
C4—C5	1.409 (5)	C11—H11B	0.9700
C4—H4	0.9300	C1—H1A	0.9700
C14—C13	1.521 (5)	C1—H1B	0.9700
C14—C15	1.549 (5)	C20—C19	1.486 (6)
C14—C5	1.555 (5)	C20—H20A	0.9600
C3—C2	1.359 (6)	C20—H20B	0.9600
C5—C6	1.382 (6)	C20—H20C	0.9600
C13—C12	1.354 (5)	C19—H19A	0.9700
C18—C12	1.447 (6)	C19—H19B	0.9700
C15—C16	1.469 (6)	C16—C17	1.093 (8)
C15—H15A	0.9700	C16—H16	0.9300
C15—H15B	0.9700	C17—H17A	0.9300
C12—C11	1.505 (5)	C17—H17B	0.9300
C13—O5—H5	109.5	C8—C9—H9B	108.9
C9—N1—C10	111.9 (3)	H9A—C9—H9B	107.7
C9—N1—C14	111.7 (3)	C3—C2—C7	121.9 (4)
C10—N1—C14	112.0 (3)	C3—C2—O2	109.8 (4)
C18—O4—C19	116.1 (3)	C7—C2—O2	128.2 (4)
C2—O2—C1	104.6 (3)	C9—C8—C6	111.8 (4)
C3—O1—C1	104.0 (3)	C9—C8—H8A	109.3
C3—C4—C5	117.6 (4)	C6—C8—H8A	109.3
C3—C4—H4	121.2	C9—C8—H8B	109.3
C5—C4—H4	121.2	C6—C8—H8B	109.3
N1—C14—C13	107.6 (3)	H8A—C8—H8B	107.9
N1—C14—C15	109.3 (3)	C2—C7—C6	117.7 (4)
C13—C14—C15	107.4 (3)	C2—C7—H7	121.2
N1—C14—C5	111.8 (3)	C6—C7—H7	121.2
C13—C14—C5	113.4 (3)	C10—C11—C12	110.5 (3)
C15—C14—C5	107.2 (3)	C10—C11—H11A	109.6
C2—C3—C4	122.1 (4)	C12—C11—H11A	109.6
C2—C3—O1	110.1 (4)	C10—C11—H11B	109.6
C4—C3—O1	127.8 (4)	C12—C11—H11B	109.6
C6—C5—C4	119.9 (4)	H11A—C11—H11B	108.1
C6—C5—C14	119.9 (3)	O2—C1—O1	108.9 (3)
C4—C5—C14	120.0 (4)	O2—C1—H1A	109.9
O5—C13—C12	121.9 (3)	O1—C1—H1A	109.9
O5—C13—C14	112.8 (3)	O2—C1—H1B	109.9
C12—C13—C14	125.2 (3)	O1—C1—H1B	109.9
O3—C18—O4	121.5 (4)	H1A—C1—H1B	108.3
O3—C18—C12	125.4 (4)	C5—C6—C7	120.8 (4)
O4—C18—C12	113.1 (4)	C5—C6—C8	122.5 (4)
C16—C15—C14	114.6 (4)	C7—C6—C8	116.7 (4)
C16—C15—H15A	108.6	C19—C20—H20A	109.5
C14—C15—H15A	108.6	C19—C20—H20B	109.5
C16—C15—H15B	108.6	H20A—C20—H20B	109.5
C14—C15—H15B	108.6	C19—C20—H20C	109.5
H15A—C15—H15B	107.6	H20A—C20—H20C	109.5
C13—C12—C18	119.0 (4)	H20B—C20—H20C	109.5
C13—C12—C11	120.3 (4)	O4—C19—C20	106.9 (4)
C18—C12—C11	120.7 (4)	O4—C19—H19A	110.3
N1—C10—C11	109.4 (3)	C20—C19—H19A	110.3
N1—C10—H10A	109.8	O4—C19—H19B	110.3
C11—C10—H10A	109.8	C20—C19—H19B	110.3
N1—C10—H10B	109.8	H19A—C19—H19B	108.6
C11—C10—H10B	109.8	C17—C16—C15	137.1 (7)
H10A—C10—H10B	108.2	C17—C16—H16	111.4
N1—C9—C8	113.2 (4)	C15—C16—H16	111.4
N1—C9—H9A	108.9	C16—C17—H17A	120.0
C8—C9—H9A	108.9	C16—C17—H17B	120.0
N1—C9—H9B	108.9	H17A—C17—H17B	120.0
C9—N1—C14—C13	−174.5 (3)	O3—C18—C12—C13	−5.7 (7)
C10—N1—C14—C13	−48.0 (4)	O4—C18—C12—C13	172.6 (4)
C9—N1—C14—C15	69.1 (4)	O3—C18—C12—C11	176.9 (4)
C10—N1—C14—C15	−164.4 (3)	O4—C18—C12—C11	−4.8 (6)
C9—N1—C14—C5	−49.4 (4)	C9—N1—C10—C11	−162.8 (3)
C10—N1—C14—C5	77.1 (4)	C14—N1—C10—C11	70.8 (4)
C5—C4—C3—C2	2.5 (6)	C10—N1—C9—C8	−63.4 (5)
C5—C4—C3—O1	179.6 (4)	C14—N1—C9—C8	63.1 (5)
C1—O1—C3—C2	−8.9 (5)	C4—C3—C2—C7	−1.1 (7)
C1—O1—C3—C4	173.6 (4)	O1—C3—C2—C7	−178.8 (4)
C3—C4—C5—C6	−2.5 (6)	C4—C3—C2—O2	176.9 (4)
C3—C4—C5—C14	−177.0 (3)	O1—C3—C2—O2	−0.7 (5)
N1—C14—C5—C6	21.5 (5)	C1—O2—C2—C3	10.2 (5)
C13—C14—C5—C6	143.4 (4)	C1—O2—C2—C7	−171.9 (5)
C15—C14—C5—C6	−98.2 (4)	N1—C9—C8—C6	−44.0 (6)
N1—C14—C5—C4	−163.9 (3)	C3—C2—C7—C6	−0.2 (8)
C13—C14—C5—C4	−42.1 (5)	O2—C2—C7—C6	−177.9 (5)
C15—C14—C5—C4	76.3 (4)	N1—C10—C11—C12	−49.7 (5)
N1—C14—C13—O5	−165.2 (3)	C13—C12—C11—C10	13.8 (5)
C15—C14—C13—O5	−47.7 (4)	C18—C12—C11—C10	−168.8 (4)
C5—C14—C13—O5	70.6 (4)	C2—O2—C1—O1	−15.8 (5)
N1—C14—C13—C12	10.8 (5)	C3—O1—C1—O2	15.3 (5)
C15—C14—C13—C12	128.3 (4)	C4—C5—C6—C7	1.2 (7)
C5—C14—C13—C12	−113.4 (4)	C14—C5—C6—C7	175.8 (4)
C19—O4—C18—O3	0.4 (6)	C4—C5—C6—C8	−179.9 (4)
C19—O4—C18—C12	−178.0 (4)	C14—C5—C6—C8	−5.4 (7)
N1—C14—C15—C16	55.0 (5)	C2—C7—C6—C5	0.1 (8)
C13—C14—C15—C16	−61.4 (5)	C2—C7—C6—C8	−178.8 (5)
C5—C14—C15—C16	176.4 (4)	C9—C8—C6—C5	15.8 (7)
O5—C13—C12—C18	4.0 (6)	C9—C8—C6—C7	−165.3 (5)
C14—C13—C12—C18	−171.7 (4)	C18—O4—C19—C20	178.2 (4)
O5—C13—C12—C11	−178.6 (4)	C14—C15—C16—C17	144.5 (11)
C14—C13—C12—C11	5.7 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O3	0.82	1.83	2.556 (4)	147