(3S,4R)-4-[4-(Benz­yloxy)phen­yl]-3-(4-fluoro­phen­yl)-1-[(S)-1-(4-methoxy­phen­yl)eth­yl]azetidin-2-one

The title compound, C₃₁H₂₈FNO₃, is an inter­mediate in the synthesis of ezetimibe analogues. The absolute configuration has been established on the basis of an unchanging chiral centre in one reactant.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.046
• wR factor = 0.133
• Data-to-parameter ratio = 9.2

checkCIF/PLATON results

No syntax errors found



Alert level A
DIFF020_ALERT_1_A  _diffrn_standards_interval_count and
            _diffrn_standards_interval_time are missing. Number of measurements
            between standards or time (min) between standards.
DIFF022_ALERT_1_A  _diffrn_standards_decay_% is missing
            Percentage decrease in standards intensity.

Alert level B
PLAT222_ALERT_3_B Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       4.34 Ratio
PLAT230_ALERT_2_B Hirshfeld Test Diff for    O2     -   C31     ..       7.29 su

Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent .....          ?
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       3.46 Ratio
PLAT230_ALERT_2_C Hirshfeld Test Diff for    C28    -   C29     ..       6.24 su
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for         C4
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C20
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C29
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C6
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C16
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C19
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C28
PLAT331_ALERT_2_C Small Average Phenyl C-C Dist.   C1     -C6            1.36 Ang.
PLAT334_ALERT_2_C Small Average Benzene C-C Dist.  C16    -C21           1.36 Ang.
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          6

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.42
           From the CIF: _reflns_number_total               3017
           Count of symmetry unique reflns         3029
           Completeness (_total/calc)             99.60%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C14    = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C15    = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C23    = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          7

   2 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
  14 ALERT level C = Check and explain
   7 ALERT level G = General alerts; check

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

---

Computing details

Data collection: RAPID-AUTO (Rigaku, 1999); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97.

(3S,4R)-4-[4-(Benzyloxy)phenyl]-3-(4-fluorophenyl)-1-[(S)-1-(4-methoxyphenyl)ethyl]azetidin-2-one

Crystal data

C31H28FNO3	F(000) = 508
Mr = 481.54	Dx = 1.251 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 8119 reflections
a = 5.9709 (12) Å	θ = 3.9–54.7°
b = 14.377 (3) Å	µ = 0.09 mm^−1
c = 14.905 (3) Å	T = 293 K
β = 92.64 (3)°	Block, colourless
V = 1278.2 (4) Å^3	0.31 × 0.31 × 0.28 mm
Z = 2

Data collection

Rigaku R-AXIS RAPID diffractometer	3017 independent reflections
Radiation source: fine-focus sealed tube	1770 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
φ scans	θmax = 27.4°, θmin = 1.4°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	h = 0→7
Tmin = 0.974, Tmax = 0.977	k = 0→18
6874 measured reflections	l = −19→19

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)] = 0.046	H-atom parameters constrained
wR(F^2) = 0.133	w = 1/[σ^2(Fo^2) + (0.0774P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.93	(Δ/σ)max < 0.001
3017 reflections	Δρmax = 0.16 e Å^−3
327 parameters	Δρmin = −0.14 e Å^−3
7 restraints	Absolute structure: assigned on the basis of unchanging chiral centre
Primary atom site location: structure-invariant direct methods

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
C31	0.7798 (15)	0.2008 (7)	1.0079 (4)	0.162 (3)
H31A	0.9255	0.1805	0.9914	0.243*
H31B	0.7558	0.1823	1.0686	0.243*
H31C	0.7706	0.2673	1.0033	0.243*
C24	0.8011 (7)	0.1990 (3)	0.5265 (3)	0.0748 (12)
H24A	0.7814	0.2086	0.4629	0.112*
H24B	0.8228	0.1340	0.5385	0.112*
H24C	0.9299	0.2332	0.5491	0.112*
O3	0.2283 (4)	0.3777 (2)	0.61687 (16)	0.0653 (7)
C14	0.7188 (5)	0.4058 (2)	0.5249 (2)	0.0471 (7)
H14	0.8547	0.4101	0.5642	0.056*
O1	0.8946 (4)	0.4173 (2)	0.15570 (17)	0.0695 (7)
C8	0.8670 (6)	0.4157 (3)	0.2458 (2)	0.0549 (9)
C7	1.0886 (7)	0.4603 (4)	0.1244 (3)	0.0777 (12)
H7A	1.2216	0.4316	0.1520	0.093*
H7B	1.0896	0.5258	0.1402	0.093*
N1	0.5647 (4)	0.3323 (2)	0.55505 (18)	0.0514 (7)
C10	0.9696 (5)	0.4427 (3)	0.4002 (2)	0.0559 (9)
H10	1.0733	0.4649	0.4435	0.067*
C13	0.6698 (6)	0.3753 (3)	0.2720 (2)	0.0639 (10)
H13	0.5681	0.3514	0.2288	0.077*
C11	0.7720 (5)	0.4043 (2)	0.4276 (2)	0.0477 (7)
C22	0.4059 (5)	0.3909 (3)	0.5821 (2)	0.0511 (8)
C15	0.5350 (5)	0.4770 (2)	0.5526 (2)	0.0481 (8)
H15	0.4611	0.5061	0.4997	0.058*
C25	0.5997 (6)	0.2117 (2)	0.6718 (3)	0.0586 (9)
C16	0.5962 (5)	0.5481 (2)	0.6234 (2)	0.0497 (8)
C12	0.6233 (6)	0.3703 (3)	0.3612 (2)	0.0615 (10)
H12	0.4892	0.3435	0.3774	0.074*
C9	1.0187 (6)	0.4493 (3)	0.3108 (2)	0.0628 (10)
H9	1.1525	0.4762	0.2945	0.075*
C6	1.0885 (7)	0.4497 (3)	0.0244 (3)	0.0680 (10)
C23	0.5944 (6)	0.2328 (2)	0.5723 (2)	0.0571 (9)
H23	0.4645	0.2005	0.5444	0.069*
F1	0.7622 (6)	0.7411 (2)	0.8164 (2)	0.1160 (11)
C1	0.9113 (8)	0.4802 (4)	−0.0296 (3)	0.0903 (14)
H1	0.7877	0.5065	−0.0036	0.108*
C27	0.7780 (9)	0.2303 (4)	0.8202 (3)	0.0932 (15)
H27	0.8947	0.2550	0.8562	0.112*
C17	0.7904 (7)	0.5974 (3)	0.6221 (3)	0.0795 (13)
H17	0.8881	0.5862	0.5765	0.095*
C30	0.4412 (8)	0.1576 (4)	0.7097 (4)	0.0872 (14)
H30	0.3266	0.1311	0.6739	0.105*
O2	0.6088 (9)	0.1586 (3)	0.9478 (3)	0.1426 (17)
C26	0.7677 (8)	0.2468 (3)	0.7279 (3)	0.0783 (12)
H26	0.8789	0.2829	0.7035	0.094*
C29	0.4519 (10)	0.1419 (5)	0.8033 (4)	0.1101 (19)
H29	0.3424	0.1057	0.8288	0.132*
C5	1.2685 (9)	0.4108 (5)	−0.0144 (4)	0.1045 (17)
H5	1.3896	0.3885	0.0207	0.125*
C18	0.8468 (8)	0.6632 (3)	0.6858 (3)	0.0884 (14)
H18	0.9791	0.6970	0.6831	0.106*
C19	0.7060 (8)	0.6775 (3)	0.7522 (3)	0.0758 (12)
C20	0.5115 (9)	0.6321 (4)	0.7555 (3)	0.0982 (16)
H20	0.4149	0.6441	0.8013	0.118*
C21	0.4555 (8)	0.5672 (3)	0.6903 (3)	0.0795 (13)
H21	0.3193	0.5361	0.6919	0.095*
C4	1.2673 (14)	0.4052 (6)	−0.1087 (5)	0.145 (3)
H4	1.3890	0.3801	−0.1370	0.174*
C28	0.6193 (10)	0.1789 (4)	0.8567 (4)	0.0919 (14)
C3	1.0838 (17)	0.4373 (6)	−0.1583 (4)	0.131 (3)
H3	1.0818	0.4337	−0.2206	0.158*
C2	0.9131 (13)	0.4726 (5)	−0.1196 (4)	0.118 (2)
H2	0.7898	0.4929	−0.1546	0.142*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C31	0.242 (7)	0.165 (6)	0.079 (4)	0.007 (6)	−0.010 (4)	0.008 (4)
C24	0.089 (3)	0.059 (2)	0.077 (3)	0.012 (2)	0.016 (2)	−0.004 (2)
O3	0.0386 (12)	0.086 (2)	0.0716 (16)	−0.0042 (13)	0.0066 (11)	0.0039 (15)
C14	0.0391 (15)	0.0496 (18)	0.0523 (17)	−0.0009 (15)	0.0001 (13)	0.0033 (16)
O1	0.0670 (15)	0.091 (2)	0.0506 (13)	−0.0090 (15)	0.0070 (11)	0.0072 (13)
C8	0.0556 (19)	0.059 (2)	0.0505 (19)	−0.0006 (18)	0.0049 (15)	0.0057 (18)
C7	0.069 (2)	0.097 (3)	0.067 (2)	−0.013 (2)	0.009 (2)	0.013 (2)
N1	0.0460 (15)	0.0533 (17)	0.0552 (16)	−0.0032 (14)	0.0056 (13)	0.0060 (14)
C10	0.0445 (17)	0.068 (2)	0.055 (2)	−0.0089 (17)	0.0002 (15)	−0.0001 (17)
C13	0.054 (2)	0.084 (3)	0.053 (2)	−0.012 (2)	−0.0061 (16)	−0.001 (2)
C11	0.0405 (16)	0.0531 (19)	0.0496 (17)	−0.0025 (16)	0.0022 (13)	0.0015 (17)
C22	0.0392 (17)	0.065 (2)	0.0487 (17)	−0.0002 (17)	−0.0042 (14)	0.0034 (17)
C15	0.0397 (16)	0.056 (2)	0.0480 (18)	0.0052 (15)	0.0016 (13)	0.0058 (16)
C25	0.058 (2)	0.0428 (19)	0.076 (2)	−0.0049 (17)	0.0117 (18)	0.0037 (18)
C16	0.0491 (19)	0.0481 (19)	0.0522 (19)	0.0063 (15)	0.0049 (15)	0.0057 (16)
C12	0.0456 (17)	0.082 (3)	0.057 (2)	−0.0151 (19)	0.0006 (16)	0.002 (2)
C9	0.0483 (18)	0.078 (3)	0.062 (2)	−0.0111 (19)	0.0051 (16)	0.005 (2)
C6	0.070 (2)	0.072 (3)	0.064 (2)	−0.001 (2)	0.018 (2)	0.010 (2)
C23	0.057 (2)	0.049 (2)	0.065 (2)	−0.0097 (16)	0.0013 (17)	−0.0058 (17)
F1	0.143 (3)	0.092 (2)	0.113 (2)	0.0051 (19)	−0.0039 (19)	−0.0475 (19)
C1	0.099 (3)	0.096 (4)	0.076 (3)	0.019 (3)	−0.003 (3)	0.009 (3)
C27	0.122 (4)	0.079 (3)	0.077 (3)	−0.017 (3)	−0.008 (3)	0.015 (3)
C17	0.073 (3)	0.090 (3)	0.076 (3)	−0.017 (2)	0.021 (2)	−0.019 (2)
C30	0.074 (3)	0.081 (3)	0.107 (4)	−0.018 (3)	0.016 (2)	0.021 (3)
O2	0.214 (5)	0.123 (4)	0.094 (3)	0.015 (3)	0.044 (3)	0.046 (3)
C26	0.092 (3)	0.075 (3)	0.067 (3)	−0.022 (2)	0.001 (2)	0.016 (2)
C29	0.112 (4)	0.097 (4)	0.125 (5)	−0.009 (4)	0.055 (4)	0.041 (4)
C5	0.090 (3)	0.123 (5)	0.102 (4)	0.010 (3)	0.025 (3)	0.003 (4)
C18	0.078 (3)	0.082 (3)	0.105 (3)	−0.015 (3)	0.010 (3)	−0.027 (3)
C19	0.092 (3)	0.060 (2)	0.076 (3)	0.009 (2)	−0.004 (2)	−0.019 (2)
C20	0.118 (4)	0.087 (3)	0.094 (3)	−0.008 (3)	0.041 (3)	−0.030 (3)
C21	0.079 (3)	0.075 (3)	0.087 (3)	−0.010 (2)	0.031 (2)	−0.015 (3)
C4	0.152 (6)	0.152 (7)	0.139 (6)	−0.048 (6)	0.092 (5)	−0.049 (6)
C28	0.123 (4)	0.066 (3)	0.089 (3)	0.007 (3)	0.024 (3)	0.021 (3)
C3	0.184 (7)	0.148 (7)	0.065 (3)	−0.091 (6)	0.028 (4)	−0.008 (4)
C2	0.152 (6)	0.125 (5)	0.076 (4)	−0.025 (5)	−0.009 (4)	0.029 (4)

Geometric parameters (Å, º)

C31—O2	1.459 (9)	C16—C21	1.360 (5)
C31—H31A	0.960	C16—C17	1.360 (5)
C31—H31B	0.960	C12—H12	0.930
C31—H31C	0.960	C9—H9	0.930
C24—C23	1.517 (5)	C6—C5	1.364 (6)
C24—H24A	0.960	C6—C1	1.371 (5)
C24—H24B	0.960	C23—H23	0.980
C24—H24C	0.960	F1—C19	1.354 (5)
O3—C22	1.217 (4)	C1—C2	1.346 (8)
C14—N1	1.484 (4)	C1—H1	0.930
C14—C11	1.500 (4)	C27—C28	1.338 (7)
C14—C15	1.569 (4)	C27—C26	1.394 (6)
C14—H14	0.980	C27—H27	0.930
O1—C8	1.360 (4)	C17—C18	1.371 (6)
O1—C7	1.411 (5)	C17—H17	0.930
C8—C9	1.383 (5)	C30—C29	1.412 (7)
C8—C13	1.386 (5)	C30—H30	0.930
C7—C6	1.498 (6)	O2—C28	1.393 (6)
C7—H7A	0.970	C26—H26	0.930
C7—H7B	0.970	C29—C28	1.357 (8)
N1—C22	1.343 (4)	C29—H29	0.930
N1—C23	1.463 (5)	C5—C4	1.407 (9)
C10—C9	1.380 (5)	C5—H5	0.930
C10—C11	1.382 (4)	C18—C19	1.344 (6)
C10—H10	0.930	C18—H18	0.930
C13—C12	1.372 (5)	C19—C20	1.335 (6)
C13—H13	0.930	C20—C21	1.377 (7)
C11—C12	1.388 (5)	C20—H20	0.930
C22—C15	1.533 (5)	C21—H21	0.930
C15—C16	1.503 (5)	C4—C3	1.373 (11)
C15—H15	0.980	C4—H4	0.930
C25—C30	1.367 (5)	C3—C2	1.297 (10)
C25—C26	1.372 (5)	C3—H3	0.930
C25—C23	1.513 (5)	C2—H2	0.930
O2—C31—H31A	109.5	C10—C9—C8	119.4 (3)
O2—C31—H31B	109.5	C10—C9—H9	120.3
H31A—C31—H31B	109.5	C8—C9—H9	120.3
O2—C31—H31C	109.5	C5—C6—C1	118.9 (4)
H31A—C31—H31C	109.5	C5—C6—C7	120.0 (4)
H31B—C31—H31C	109.5	C1—C6—C7	121.1 (4)
C23—C24—H24A	109.5	N1—C23—C25	111.4 (3)
C23—C24—H24B	109.5	N1—C23—C24	109.2 (3)
H24A—C24—H24B	109.5	C25—C23—C24	113.3 (3)
C23—C24—H24C	109.5	N1—C23—H23	107.6
H24A—C24—H24C	109.5	C25—C23—H23	107.6
H24B—C24—H24C	109.5	C24—C23—H23	107.6
N1—C14—C11	116.3 (3)	C2—C1—C6	121.2 (5)
N1—C14—C15	86.2 (2)	C2—C1—H1	119.4
C11—C14—C15	116.5 (3)	C6—C1—H1	119.4
N1—C14—H14	111.8	C28—C27—C26	119.7 (5)
C11—C14—H14	111.8	C28—C27—H27	120.1
C15—C14—H14	111.8	C26—C27—H27	120.1
C8—O1—C7	118.2 (3)	C16—C17—C18	122.1 (4)
O1—C8—C9	125.5 (3)	C16—C17—H17	118.9
O1—C8—C13	115.4 (3)	C18—C17—H17	118.9
C9—C8—C13	119.1 (3)	C25—C30—C29	119.9 (5)
O1—C7—C6	108.8 (3)	C25—C30—H30	120.1
O1—C7—H7A	109.9	C29—C30—H30	120.1
C6—C7—H7A	109.9	C28—O2—C31	116.8 (5)
O1—C7—H7B	109.9	C25—C26—C27	122.4 (4)
C6—C7—H7B	109.9	C25—C26—H26	118.8
H7A—C7—H7B	108.3	C27—C26—H26	118.8
C22—N1—C23	129.9 (3)	C28—C29—C30	121.1 (5)
C22—N1—C14	95.8 (3)	C28—C29—H29	119.5
C23—N1—C14	132.6 (3)	C30—C29—H29	119.5
C9—C10—C11	122.4 (3)	C6—C5—C4	118.6 (6)
C9—C10—H10	118.8	C6—C5—H5	120.7
C11—C10—H10	118.8	C4—C5—H5	120.7
C12—C13—C8	120.6 (3)	C19—C18—C17	118.3 (4)
C12—C13—H13	119.7	C19—C18—H18	120.9
C8—C13—H13	119.7	C17—C18—H18	120.9
C10—C11—C12	117.2 (3)	C20—C19—C18	121.8 (4)
C10—C11—C14	120.1 (3)	C20—C19—F1	119.4 (4)
C12—C11—C14	122.6 (3)	C18—C19—F1	118.7 (5)
O3—C22—N1	132.1 (4)	C19—C20—C21	119.2 (4)
O3—C22—C15	135.1 (3)	C19—C20—H20	120.4
N1—C22—C15	92.8 (2)	C21—C20—H20	120.4
C16—C15—C22	117.2 (3)	C16—C21—C20	121.1 (4)
C16—C15—C14	118.5 (3)	C16—C21—H21	119.5
C22—C15—C14	85.2 (2)	C20—C21—H21	119.5
C16—C15—H15	111.2	C3—C4—C5	119.1 (6)
C22—C15—H15	111.2	C3—C4—H4	120.5
C14—C15—H15	111.2	C5—C4—H4	120.5
C30—C25—C26	117.3 (4)	C27—C28—C29	119.6 (5)
C30—C25—C23	122.4 (4)	C27—C28—O2	125.2 (6)
C26—C25—C23	120.4 (3)	C29—C28—O2	115.1 (5)
C21—C16—C17	117.4 (4)	C2—C3—C4	121.1 (6)
C21—C16—C15	120.9 (3)	C2—C3—H3	119.5
C17—C16—C15	121.6 (3)	C4—C3—H3	119.5
C13—C12—C11	121.4 (3)	C3—C2—C1	121.1 (7)
C13—C12—H12	119.3	C3—C2—H2	119.4
C11—C12—H12	119.3	C1—C2—H2	119.4