Trimethyl 5-(2-chloro-4-fluoro-phen-yl)-2-phenyl-pyrrolidine-2,3,4-tricarboxyl-ate.

The title compound, C(22)H(21)ClFNO(6), was synthesized by the 1,3-dipolar cyclo-addition reaction of dimethyl maleate, methyl 2-amino-2-phenyl-acetate and 2-chloro-4-fluoro-benzaldehyde. The pyrrolidine ring possesses an envelope conformation and the two benzene rings are oriented at a dihedral angle of 68.28 (7)°. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure. One methyl group is disordered over two positions with a site-occupancy ratio of 0.651 (12):0.349 (12).

Related literature

For the biological activity of pyrrolidine derivatives, see: Coldham & Hufton (2005 ▶); Nair & Suja (2007 ▶); Pandey et al. (2006 ▶); Sardina & Rapoport (1996 ▶); Witherup et al. (1995 ▶). For a related structure, see: Yu et al. (2007 ▶).

Experimental

Crystal data

C22H21ClFNO6

M = 449.85

Orthorhombic,

a = 9.474 (3) Å

b = 15.057 (8) Å

c = 15.182 (5) Å

V = 2165.7 (15) Å3

Z = 4

Cu Kα radiation

μ = 1.98 mm−1

T = 298 K

0.38 × 0.36 × 0.03 mm

Data collection

Oxford Diffraction Gemini S Ultra diffractometer

Absorption correction: multi-scan (CrysAlis Pro; Oxford Diffraction, 2009 ▶) T min = 0.520, T max = 0.943

32943 measured reflections

3442 independent reflections

3332 reflections with I > 2σ(I)

R int = 0.025

Refinement

R[F 2 > 2σ(F 2)] = 0.024

wR(F 2) = 0.060

S = 1.05

3442 reflections

290 parameters

1 restraint

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.12 e Å−3

Δρmin = −0.16 e Å−3

Absolute structure: Flack (1983 ▶), 1456 Friedel pairs

Flack parameter: −0.001 (11)

Data collection: CrysAlis Pro (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis Pro; data reduction: CrysAlis Pro; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809044274/xu2655sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809044274/xu2655Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C22H21ClFNO6	F(000) = 936
Mr = 449.85	Dx = 1.380 Mg m−3
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: P 2ac 2ab	Cell parameters from 23516 reflections
a = 9.474 (3) Å	θ = 2.9–62.8°
b = 15.057 (8) Å	µ = 1.98 mm−1
c = 15.182 (5) Å	T = 298 K
V = 2165.7 (15) Å3	Platelet, colourless
Z = 4	0.38 × 0.36 × 0.03 mm

Oxford Diffraction Gemini S Ultra diffractometer	3442 independent reflections
Radiation source: Enhance Ultra (Cu) X-ray Source	3332 reflections with I > 2σ(I)
mirror	Rint = 0.025
Detector resolution: 15.9149 pixels mm-1	θmax = 62.6°, θmin = 4.1°
ω scans	h = −10→10
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)	k = −17→17
Tmin = 0.520, Tmax = 0.943	l = −17→17
32943 measured reflections

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.024	w = 1/[σ2(Fo2) + (0.0318P)2 + 0.3155P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.060	(Δ/σ)max = 0.001
S = 1.05	Δρmax = 0.12 e Å−3
3442 reflections	Δρmin = −0.16 e Å−3
290 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraint	Extinction coefficient: 0.0055 (2)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 1456 Friedel pairs
Secondary atom site location: difference Fourier map	Flack parameter: −0.001 (11)

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
Cl1	0.87819 (6)	0.40571 (3)	0.69190 (3)	0.06039 (14)
F1	1.10815 (14)	0.42498 (8)	0.39470 (7)	0.0789 (4)
O1	0.64936 (15)	0.70388 (7)	0.55124 (8)	0.0578 (3)
O2	0.59938 (18)	0.55992 (8)	0.53671 (8)	0.0715 (4)
O3	0.50206 (14)	0.80786 (9)	0.73253 (11)	0.0735 (4)
O4	0.41937 (11)	0.67622 (8)	0.68953 (9)	0.0568 (3)
O5	0.79799 (13)	0.86655 (7)	0.67762 (8)	0.0553 (3)
O6	0.74501 (13)	0.87248 (7)	0.82137 (7)	0.0509 (3)
N1	0.89048 (14)	0.69866 (8)	0.69034 (9)	0.0390 (3)
H1	0.870 (2)	0.7278 (11)	0.6438 (12)	0.047*
C1	1.0498 (2)	0.46980 (13)	0.46390 (11)	0.0546 (4)
C2	1.00115 (19)	0.42137 (12)	0.53368 (11)	0.0500 (4)
H2	1.0094	0.3598	0.5350	0.060*
C3	0.93922 (17)	0.46752 (10)	0.60228 (10)	0.0417 (4)
C4	0.92532 (15)	0.55915 (10)	0.60251 (10)	0.0386 (3)
C5	0.98023 (19)	0.60471 (12)	0.53049 (11)	0.0509 (4)
H5	0.9745	0.6664	0.5293	0.061*
C6	1.0431 (2)	0.56086 (13)	0.46054 (12)	0.0588 (5)
H6	1.0796	0.5921	0.4128	0.071*
C7	0.85178 (16)	0.60535 (9)	0.67778 (9)	0.0379 (3)
H7	0.8783	0.5738	0.7318	0.045*
C8	0.68738 (15)	0.60534 (10)	0.67347 (10)	0.0393 (3)
H8	0.6491	0.5473	0.6902	0.047*
C9	0.65018 (15)	0.67691 (10)	0.74326 (10)	0.0390 (3)
H9	0.6296	0.6450	0.7980	0.047*
C10	0.79423 (16)	0.72962 (10)	0.75935 (10)	0.0372 (3)
C11	0.85468 (17)	0.70603 (9)	0.85036 (10)	0.0386 (3)
C12	0.99477 (17)	0.68067 (11)	0.86012 (11)	0.0468 (4)
H12	1.0537	0.6788	0.8111	0.056*
C13	1.0475 (2)	0.65805 (12)	0.94231 (13)	0.0589 (5)
H13	1.1410	0.6401	0.9477	0.071*
C14	0.9633 (2)	0.66181 (12)	1.01602 (12)	0.0604 (5)
H14	0.9992	0.6464	1.0710	0.073*
C15	0.8256 (2)	0.68856 (12)	1.00731 (12)	0.0565 (5)
H15	0.7685	0.6928	1.0569	0.068*
C16	0.77124 (19)	0.70915 (11)	0.92558 (11)	0.0478 (4)
H16	0.6769	0.7254	0.9207	0.057*
C17	0.77865 (16)	0.83067 (10)	0.74725 (11)	0.0409 (3)
C18	0.7123 (2)	0.96590 (11)	0.81177 (15)	0.0666 (5)
H18A	0.7012	0.9922	0.8690	0.100*
H18B	0.6263	0.9724	0.7790	0.100*
H18C	0.7878	0.9950	0.7810	0.100*
C19	0.51912 (18)	0.73007 (12)	0.72121 (11)	0.0462 (4)
C20	0.2893 (2)	0.71857 (16)	0.66086 (19)	0.0810 (7)
H20A	0.2229	0.6739	0.6429	0.121*
H20B	0.3088	0.7573	0.6121	0.121*
H20C	0.2502	0.7524	0.7086	0.121*
C21	0.64215 (18)	0.63050 (10)	0.58152 (10)	0.0442 (4)
C22A	0.5863 (10)	0.5705 (4)	0.4390 (3)	0.0813 (19)	0.651 (12)
H22A	0.6715	0.5505	0.4112	0.122*	0.651 (12)
H22B	0.5708	0.6319	0.4251	0.122*	0.651 (12)
H22C	0.5081	0.5358	0.4181	0.122*	0.651 (12)
C22B	0.5167 (16)	0.5848 (8)	0.4569 (7)	0.0813 (19)	0.349 (12)
H22D	0.4260	0.6070	0.4744	0.122*	0.349 (12)
H22E	0.5046	0.5335	0.4201	0.122*	0.349 (12)
H22F	0.5664	0.6300	0.4248	0.122*	0.349 (12)

	U11	U22	U33	U12	U13	U23
Cl1	0.0909 (3)	0.0400 (2)	0.0503 (2)	0.0019 (2)	0.0084 (2)	0.00626 (17)
F1	0.0926 (9)	0.0837 (8)	0.0604 (6)	0.0170 (7)	0.0228 (6)	−0.0173 (6)
O1	0.0762 (9)	0.0468 (7)	0.0505 (7)	−0.0035 (6)	−0.0099 (6)	0.0073 (5)
O2	0.1081 (12)	0.0502 (7)	0.0562 (7)	−0.0174 (7)	−0.0325 (7)	0.0010 (6)
O3	0.0495 (7)	0.0544 (8)	0.1167 (13)	0.0096 (6)	−0.0117 (7)	−0.0141 (8)
O4	0.0371 (6)	0.0568 (7)	0.0766 (8)	−0.0006 (5)	−0.0088 (6)	−0.0026 (7)
O5	0.0692 (8)	0.0449 (6)	0.0519 (7)	0.0018 (5)	0.0049 (6)	0.0112 (5)
O6	0.0651 (8)	0.0368 (5)	0.0507 (6)	0.0065 (5)	−0.0016 (6)	−0.0044 (5)
N1	0.0423 (7)	0.0352 (6)	0.0393 (6)	−0.0019 (5)	0.0035 (6)	−0.0011 (5)
C1	0.0541 (10)	0.0627 (11)	0.0468 (10)	0.0104 (9)	0.0073 (8)	−0.0100 (8)
C2	0.0556 (10)	0.0442 (9)	0.0502 (9)	0.0081 (8)	−0.0030 (8)	−0.0062 (7)
C3	0.0452 (9)	0.0401 (8)	0.0399 (8)	0.0012 (7)	−0.0021 (7)	0.0014 (6)
C4	0.0372 (8)	0.0399 (8)	0.0387 (8)	0.0003 (6)	−0.0026 (6)	0.0005 (6)
C5	0.0582 (10)	0.0446 (9)	0.0499 (9)	0.0028 (8)	0.0104 (8)	0.0041 (7)
C6	0.0666 (12)	0.0620 (12)	0.0478 (10)	0.0016 (10)	0.0155 (9)	0.0046 (8)
C7	0.0412 (8)	0.0349 (7)	0.0376 (7)	−0.0011 (6)	0.0000 (6)	0.0004 (6)
C8	0.0409 (8)	0.0351 (7)	0.0419 (8)	−0.0020 (6)	−0.0008 (6)	0.0021 (6)
C9	0.0374 (8)	0.0407 (8)	0.0389 (8)	−0.0026 (7)	0.0007 (7)	0.0022 (6)
C10	0.0365 (8)	0.0372 (8)	0.0380 (8)	0.0002 (6)	0.0017 (6)	0.0001 (6)
C11	0.0420 (8)	0.0329 (7)	0.0410 (8)	−0.0010 (6)	−0.0030 (7)	0.0002 (6)
C12	0.0405 (9)	0.0459 (9)	0.0541 (10)	−0.0006 (7)	−0.0036 (7)	−0.0052 (7)
C13	0.0521 (11)	0.0548 (10)	0.0697 (12)	0.0039 (9)	−0.0210 (10)	0.0005 (9)
C14	0.0737 (14)	0.0547 (11)	0.0529 (11)	−0.0088 (10)	−0.0200 (10)	0.0087 (9)
C15	0.0655 (12)	0.0618 (10)	0.0421 (9)	−0.0092 (9)	−0.0007 (8)	0.0058 (8)
C16	0.0450 (9)	0.0541 (9)	0.0443 (9)	0.0005 (7)	0.0005 (7)	0.0030 (7)
C17	0.0386 (8)	0.0377 (8)	0.0465 (9)	−0.0006 (6)	−0.0021 (7)	0.0002 (7)
C18	0.0837 (13)	0.0395 (9)	0.0766 (13)	0.0132 (9)	−0.0060 (12)	−0.0070 (9)
C19	0.0404 (9)	0.0466 (10)	0.0517 (9)	0.0001 (7)	0.0018 (7)	−0.0010 (7)
C20	0.0436 (11)	0.0816 (15)	0.1177 (19)	0.0075 (10)	−0.0185 (12)	−0.0039 (14)
C21	0.0432 (9)	0.0443 (9)	0.0450 (8)	−0.0014 (7)	−0.0051 (7)	−0.0002 (7)
C22A	0.126 (6)	0.070 (2)	0.0474 (18)	−0.010 (3)	−0.027 (2)	−0.0089 (17)
C22B	0.126 (6)	0.070 (2)	0.0474 (18)	−0.010 (3)	−0.027 (2)	−0.0089 (17)

Cl1—C3	1.7469 (16)	C8—H8	0.9800
F1—C1	1.366 (2)	C9—C19	1.515 (2)
O1—C21	1.1987 (19)	C9—C10	1.597 (2)
O2—C21	1.325 (2)	C9—H9	0.9800
O2—C22B	1.490 (7)	C10—C11	1.537 (2)
O2—C22A	1.497 (4)	C10—C17	1.540 (2)
O3—C19	1.195 (2)	C11—C12	1.389 (2)
O4—C19	1.335 (2)	C11—C16	1.390 (2)
O4—C20	1.454 (2)	C12—C13	1.387 (3)
O5—C17	1.201 (2)	C12—H12	0.9300
O6—C17	1.3283 (19)	C13—C14	1.375 (3)
O6—C18	1.448 (2)	C13—H13	0.9300
N1—C7	1.4645 (18)	C14—C15	1.371 (3)
N1—C10	1.465 (2)	C14—H14	0.9300
N1—H1	0.855 (18)	C15—C16	1.379 (2)
C1—C2	1.366 (3)	C15—H15	0.9300
C1—C6	1.373 (3)	C16—H16	0.9300
C2—C3	1.383 (2)	C18—H18A	0.9600
C2—H2	0.9300	C18—H18B	0.9600
C3—C4	1.386 (2)	C18—H18C	0.9600
C4—C5	1.392 (2)	C20—H20A	0.9600
C4—C7	1.508 (2)	C20—H20B	0.9600
C5—C6	1.385 (2)	C20—H20C	0.9600
C5—H5	0.9300	C22A—H22A	0.9600
C6—H6	0.9300	C22A—H22B	0.9600
C7—C8	1.559 (2)	C22A—H22C	0.9600
C7—H7	0.9800	C22B—H22D	0.9600
C8—C21	1.509 (2)	C22B—H22E	0.9600
C8—C9	1.552 (2)	C22B—H22F	0.9600
C21—O2—C22B	112.1 (5)	C12—C11—C10	121.02 (14)
C21—O2—C22A	116.7 (3)	C16—C11—C10	121.26 (14)
C22B—O2—C22A	28.9 (4)	C13—C12—C11	120.50 (17)
C19—O4—C20	116.19 (15)	C13—C12—H12	119.7
C17—O6—C18	115.25 (14)	C11—C12—H12	119.7
C7—N1—C10	104.04 (11)	C14—C13—C12	120.89 (17)
C7—N1—H1	109.1 (12)	C14—C13—H13	119.6
C10—N1—H1	106.6 (12)	C12—C13—H13	119.6
F1—C1—C2	117.99 (17)	C15—C14—C13	119.02 (17)
F1—C1—C6	118.91 (17)	C15—C14—H14	120.5
C2—C1—C6	123.10 (16)	C13—C14—H14	120.5
C1—C2—C3	117.32 (16)	C14—C15—C16	120.55 (18)
C1—C2—H2	121.3	C14—C15—H15	119.7
C3—C2—H2	121.3	C16—C15—H15	119.7
C2—C3—C4	122.85 (15)	C15—C16—C11	121.28 (17)
C2—C3—Cl1	117.35 (12)	C15—C16—H16	119.4
C4—C3—Cl1	119.79 (12)	C11—C16—H16	119.4
C3—C4—C5	116.95 (14)	O5—C17—O6	124.68 (14)
C3—C4—C7	120.33 (13)	O5—C17—C10	122.33 (14)
C5—C4—C7	122.72 (14)	O6—C17—C10	112.97 (13)
C6—C5—C4	121.88 (16)	O6—C18—H18A	109.5
C6—C5—H5	119.1	O6—C18—H18B	109.5
C4—C5—H5	119.1	H18A—C18—H18B	109.5
C1—C6—C5	117.86 (17)	O6—C18—H18C	109.5
C1—C6—H6	121.1	H18A—C18—H18C	109.5
C5—C6—H6	121.1	H18B—C18—H18C	109.5
N1—C7—C4	115.18 (12)	O3—C19—O4	123.47 (16)
N1—C7—C8	104.82 (12)	O3—C19—C9	126.67 (16)
C4—C7—C8	115.45 (12)	O4—C19—C9	109.81 (14)
N1—C7—H7	107.0	O4—C20—H20A	109.5
C4—C7—H7	107.0	O4—C20—H20B	109.5
C8—C7—H7	107.0	H20A—C20—H20B	109.5
C21—C8—C9	113.13 (12)	O4—C20—H20C	109.5
C21—C8—C7	108.82 (12)	H20A—C20—H20C	109.5
C9—C8—C7	101.43 (11)	H20B—C20—H20C	109.5
C21—C8—H8	111.0	O1—C21—O2	124.03 (15)
C9—C8—H8	111.0	O1—C21—C8	124.77 (14)
C7—C8—H8	111.0	O2—C21—C8	111.13 (13)
C19—C9—C8	113.72 (13)	O2—C22A—H22A	109.5
C19—C9—C10	118.14 (13)	O2—C22A—H22B	109.5
C8—C9—C10	104.80 (12)	H22A—C22A—H22B	109.5
C19—C9—H9	106.5	O2—C22A—H22C	109.5
C8—C9—H9	106.5	H22A—C22A—H22C	109.5
C10—C9—H9	106.5	H22B—C22A—H22C	109.5
N1—C10—C11	109.71 (12)	O2—C22B—H22D	109.5
N1—C10—C17	106.78 (12)	O2—C22B—H22E	109.5
C11—C10—C17	111.80 (12)	H22D—C22B—H22E	109.5
N1—C10—C9	105.33 (12)	O2—C22B—H22F	109.5
C11—C10—C9	109.94 (12)	H22D—C22B—H22F	109.5
C17—C10—C9	113.00 (12)	H22E—C22B—H22F	109.5
C12—C11—C16	117.72 (15)
F1—C1—C2—C3	−178.45 (16)	N1—C10—C11—C12	14.85 (19)
C6—C1—C2—C3	1.8 (3)	C17—C10—C11—C12	−103.41 (16)
C1—C2—C3—C4	0.0 (3)	C9—C10—C11—C12	130.23 (15)
C1—C2—C3—Cl1	−179.53 (14)	N1—C10—C11—C16	−165.02 (14)
C2—C3—C4—C5	−1.5 (2)	C17—C10—C11—C16	76.71 (18)
Cl1—C3—C4—C5	177.95 (12)	C9—C10—C11—C16	−49.64 (18)
C2—C3—C4—C7	177.68 (14)	C16—C11—C12—C13	1.0 (2)
Cl1—C3—C4—C7	−2.8 (2)	C10—C11—C12—C13	−178.87 (15)
C3—C4—C5—C6	1.5 (3)	C11—C12—C13—C14	−1.2 (3)
C7—C4—C5—C6	−177.73 (16)	C12—C13—C14—C15	−0.1 (3)
F1—C1—C6—C5	178.39 (17)	C13—C14—C15—C16	1.7 (3)
C2—C1—C6—C5	−1.9 (3)	C14—C15—C16—C11	−1.9 (3)
C4—C5—C6—C1	0.2 (3)	C12—C11—C16—C15	0.6 (2)
C10—N1—C7—C4	173.79 (12)	C10—C11—C16—C15	−179.57 (15)
C10—N1—C7—C8	45.80 (14)	C18—O6—C17—O5	8.4 (2)
C3—C4—C7—N1	156.57 (14)	C18—O6—C17—C10	−172.84 (15)
C5—C4—C7—N1	−24.3 (2)	N1—C10—C17—O5	24.6 (2)
C3—C4—C7—C8	−80.97 (18)	C11—C10—C17—O5	144.60 (15)
C5—C4—C7—C8	98.19 (18)	C9—C10—C17—O5	−90.74 (18)
N1—C7—C8—C21	81.72 (14)	N1—C10—C17—O6	−154.16 (13)
C4—C7—C8—C21	−46.10 (17)	C11—C10—C17—O6	−34.15 (18)
N1—C7—C8—C9	−37.78 (14)	C9—C10—C17—O6	90.51 (15)
C4—C7—C8—C9	−165.60 (12)	C20—O4—C19—O3	5.6 (3)
C21—C8—C9—C19	30.15 (18)	C20—O4—C19—C9	−176.82 (16)
C7—C8—C9—C19	146.52 (13)	C8—C9—C19—O3	−140.85 (18)
C21—C8—C9—C10	−100.31 (14)	C10—C9—C19—O3	−17.4 (3)
C7—C8—C9—C10	16.07 (14)	C8—C9—C19—O4	41.67 (18)
C7—N1—C10—C11	84.15 (14)	C10—C9—C19—O4	165.13 (13)
C7—N1—C10—C17	−154.52 (12)	C22B—O2—C21—O1	−19.4 (7)
C7—N1—C10—C9	−34.13 (14)	C22A—O2—C21—O1	12.0 (5)
C19—C9—C10—N1	−117.73 (14)	C22B—O2—C21—C8	163.6 (7)
C8—C9—C10—N1	10.09 (15)	C22A—O2—C21—C8	−165.1 (5)
C19—C9—C10—C11	124.14 (14)	C9—C8—C21—O1	38.7 (2)
C8—C9—C10—C11	−108.04 (13)	C7—C8—C21—O1	−73.2 (2)
C19—C9—C10—C17	−1.53 (19)	C9—C8—C21—O2	−144.27 (15)
C8—C9—C10—C17	126.29 (13)	C7—C8—C21—O2	103.82 (16)

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6···O5i	0.93	2.56	3.380 (3)	147

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯O5i	0.93	2.56	3.380 (3)	147

Symmetry code: (i) .