(S)-1-[3,5-Bis-(trifluoro-meth-yl)phen-yl]-N-methylethyl-amine-(R)-2-hydroxy-butane-dioic acid (1/1).

In the title compound, C(11)H(11)F(6)N·C(4)H(6)O(5), a key inter-mediate in the synthesis of the NK1 receptor antagonist of casopitant, the F atoms of the trifluoro-methyl groups are disordered over two sites with equal occupancies. In the crystal, the components are linked by bifurcated N-H⋯(O,O) hydrogen bonds.

Related literature

The title compound is a key intermediate for the synthesis of casopitant, which is an NK1 receptor antagonist (Humphrey, 2003 ▶) for the treatment of chemotheraphy-induced nausea and vomiting (CINV) (Lohr, 2008 ▶).

Experimental

Crystal data

C11H11F6N·C4H6O5

M = 405.30

Monoclinic,

a = 6.6770 (13) Å

b = 8.4510 (17) Å

c = 16.366 (3) Å

β = 100.05 (3)°

V = 909.3 (3) Å3

Z = 2

Mo Kα radiation

μ = 0.15 mm−1

T = 298 (2) K

0.30 × 0.10 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

Absorption correction: ψ scan (North et al., 1968 ▶) T min = 0.957, T max = 0.985

1915 measured reflections

1757 independent reflections

1067 reflections with I > 2σ(I)

R int = 0.058

3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.063

wR(F 2) = 0.154

S = 1.00

1757 reflections

220 parameters

2 restraints

H-atom parameters constrained

Δρmax = 0.18 e Å−3

Δρmin = −0.27 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius,1989 ▶); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); 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: SHELXL97.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808043201/at2692sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808043201/at2692Isup2.hkl

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

C11H11F6N·C4H6O5	F(000) = 416
Mr = 405.30	Dx = 1.480 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 25 reflections
a = 6.6770 (13) Å	θ = 9–12°
b = 8.4510 (17) Å	µ = 0.15 mm−1
c = 16.366 (3) Å	T = 298 K
β = 100.05 (3)°	Needle, colourless
V = 909.3 (3) Å3	0.30 × 0.10 × 0.10 mm
Z = 2

Enraf–Nonius CAD-4 diffractometer	1067 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.058
graphite	θmax = 25.3°, θmin = 1.3°
ω/2θ scans	h = 0→7
Absorption correction: ψ scan (North et al., 1968)	k = 0→10
Tmin = 0.957, Tmax = 0.985	l = −19→19
1915 measured reflections	3 standard reflections every 200 reflections
1757 independent reflections	intensity decay: 1%

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)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.154	H-atom parameters constrained
S = 1.00	w = 1/[σ2(Fo2) + (0.060P)2 + 0.3P] where P = (Fo2 + 2Fc2)/3
1757 reflections	(Δ/σ)max < 0.001
220 parameters	Δρmax = 0.18 e Å−3
2 restraints	Δρmin = −0.27 e Å−3

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)
F1	0.9058 (17)	0.4852 (16)	0.9973 (8)	0.112	0.50
F3	0.9270 (13)	0.6270 (13)	0.8772 (6)	0.083	0.50
F2	1.0892 (15)	0.4013 (14)	0.9084 (6)	0.101	0.50
F1'	0.7985 (16)	0.6070 (16)	0.9651 (7)	0.111	0.50
F2'	1.000 (2)	0.4376 (16)	0.9758 (7)	0.111	0.50
F3'	0.9991 (17)	0.5461 (16)	0.8769 (7)	0.115	0.50
F4	0.5055 (13)	−0.0158 (14)	0.9651 (7)	0.085	0.50
F5	0.3781 (15)	−0.0926 (12)	0.8429 (6)	0.080	0.50
F6	0.6975 (13)	−0.0918 (12)	0.8664 (6)	0.078	0.50
F4'	0.5831 (15)	−0.0443 (15)	0.9665 (8)	0.097	0.50
F5'	0.3083 (15)	−0.0556 (14)	0.8707 (6)	0.095	0.50
F6'	0.6174 (16)	−0.1374 (14)	0.8609 (7)	0.093	0.50
N	0.3387 (7)	0.3503 (6)	0.6045 (3)	0.0464 (12)
H0A	0.2534	0.2888	0.5744	0.056*
C1	0.8859 (12)	0.4933 (11)	0.9164 (5)	0.081
C2	0.5244 (14)	−0.0104 (14)	0.8816 (5)	0.094 (3)
C3	0.5326 (11)	0.1454 (10)	0.8548 (4)	0.063 (2)
C4	0.4157 (10)	0.2037 (8)	0.7869 (4)	0.0543 (17)
H4A	0.3136	0.1408	0.7574	0.065*
C5	0.4445 (9)	0.3611 (9)	0.7587 (4)	0.0527 (16)
C6	0.5931 (11)	0.4465 (10)	0.8000 (4)	0.072 (2)
H6A	0.6137	0.5488	0.7821	0.087*
C7	0.7249 (13)	0.3856 (12)	0.8723 (5)	0.080 (2)
C8	0.6962 (12)	0.2426 (12)	0.8978 (5)	0.079 (3)
H8A	0.7817	0.2026	0.9441	0.095*
C9	0.3017 (8)	0.4239 (8)	0.6855 (3)	0.0482 (15)
H9A	0.3274	0.5377	0.6823	0.058*
C10	0.0783 (9)	0.4033 (9)	0.6903 (4)	0.0646 (19)
H10A	0.0507	0.4508	0.7405	0.097*
H10B	0.0461	0.2926	0.6902	0.097*
H10C	−0.0033	0.4535	0.6433	0.097*
C11	0.5373 (9)	0.3961 (9)	0.5832 (4)	0.0606 (18)
H11A	0.5542	0.3455	0.5323	0.091*
H11B	0.6447	0.3636	0.6269	0.091*
H11C	0.5419	0.5088	0.5766	0.091*
O1	0.6777 (8)	0.0742 (7)	0.6474 (4)	0.0869 (18)
O2	0.5220 (7)	−0.1471 (5)	0.6689 (3)	0.0652 (13)
H2A	0.4226	−0.0912	0.6526	0.098*
O3	0.8263 (6)	−0.2740 (5)	0.5576 (3)	0.0579 (12)
H3A	0.8825	−0.3437	0.5351	0.087*
O4	1.1965 (6)	0.0264 (5)	0.6157 (3)	0.0540 (11)
O5	0.9516 (7)	0.0076 (6)	0.5086 (3)	0.0678 (15)
H5A	1.0184	0.0743	0.4888	0.102*
C12	0.6858 (11)	−0.0671 (9)	0.6676 (4)	0.0551 (17)
C13	0.8797 (9)	−0.1508 (8)	0.6891 (4)	0.0522 (15)
H13A	0.8587	−0.2481	0.7179	0.063*
H13B	0.9744	−0.0857	0.7265	0.063*
C14	0.9715 (8)	−0.1898 (7)	0.6122 (3)	0.0428 (14)
H14A	1.0894	−0.2588	0.6292	0.051*
C15	1.0461 (9)	−0.0360 (7)	0.5766 (4)	0.0464 (15)

	U11	U22	U33	U12	U13	U23
F1	0.112	0.112	0.112	0.000	0.020	0.000
F3	0.083	0.083	0.083	0.000	0.015	0.000
F2	0.101	0.101	0.101	0.000	0.018	0.000
F1'	0.111	0.111	0.111	0.000	0.019	0.000
F2'	0.111	0.111	0.111	0.000	0.019	0.000
F3'	0.115	0.115	0.115	0.000	0.020	0.000
F4	0.085	0.085	0.085	0.000	0.015	0.000
F5	0.080	0.080	0.080	0.000	0.014	0.000
F6	0.078	0.078	0.078	0.000	0.014	0.000
F4'	0.097	0.097	0.097	0.000	0.017	0.000
F5'	0.095	0.095	0.095	0.000	0.017	0.000
F6'	0.093	0.093	0.093	0.000	0.016	0.000
N	0.050 (3)	0.044 (3)	0.047 (3)	−0.015 (3)	0.010 (2)	−0.004 (3)
C1	0.072	0.100	0.067	−0.033	−0.003	0.033
C2	0.097 (7)	0.114 (8)	0.069 (6)	0.014 (7)	0.012 (5)	0.000 (6)
C3	0.063 (4)	0.065 (5)	0.059 (4)	0.016 (4)	0.005 (4)	0.000 (4)
C4	0.055 (4)	0.058 (4)	0.048 (3)	−0.002 (4)	0.002 (3)	0.002 (3)
C5	0.053 (4)	0.065 (5)	0.042 (3)	−0.004 (4)	0.013 (3)	−0.002 (3)
C6	0.075 (5)	0.084 (6)	0.055 (4)	−0.014 (5)	0.003 (4)	−0.012 (4)
C7	0.068 (5)	0.076 (6)	0.089 (6)	−0.003 (5)	−0.006 (4)	0.001 (5)
C8	0.068 (5)	0.102 (7)	0.061 (5)	0.000 (5)	−0.007 (4)	−0.014 (5)
C9	0.053 (3)	0.045 (3)	0.045 (3)	0.009 (3)	0.003 (3)	0.007 (3)
C10	0.054 (4)	0.069 (5)	0.073 (4)	0.005 (4)	0.017 (3)	0.014 (4)
C11	0.047 (3)	0.062 (4)	0.072 (4)	−0.015 (3)	0.010 (3)	0.003 (4)
O1	0.081 (4)	0.067 (4)	0.120 (5)	0.011 (3)	0.037 (3)	0.010 (4)
O2	0.068 (3)	0.053 (3)	0.074 (3)	−0.002 (3)	0.009 (2)	0.002 (3)
O3	0.059 (3)	0.043 (2)	0.074 (3)	−0.012 (2)	0.018 (2)	−0.011 (2)
O4	0.046 (2)	0.053 (3)	0.062 (3)	−0.011 (2)	0.009 (2)	−0.002 (2)
O5	0.082 (3)	0.066 (3)	0.052 (2)	−0.022 (3)	0.003 (2)	0.015 (3)
C12	0.062 (4)	0.061 (4)	0.046 (4)	−0.003 (4)	0.022 (3)	−0.005 (3)
C13	0.060 (4)	0.051 (4)	0.048 (3)	0.005 (4)	0.016 (3)	0.003 (3)
C14	0.041 (3)	0.048 (4)	0.042 (3)	0.007 (3)	0.014 (3)	0.006 (3)
C15	0.046 (3)	0.036 (3)	0.061 (4)	0.005 (3)	0.020 (3)	−0.004 (3)

F1—C1	1.309 (14)	C7—C8	1.304 (13)
F3—C1	1.352 (13)	C8—H8A	0.9300
F2—C1	1.589 (14)	C9—C10	1.517 (8)
F1'—C1	1.436 (13)	C9—H9A	0.9800
F2'—C1	1.219 (13)	C10—H10A	0.9600
F3'—C1	1.167 (12)	C10—H10B	0.9600
F4—C2	1.395 (13)	C10—H10C	0.9600
F5—C2	1.274 (12)	C11—H11A	0.9600
F6—C2	1.404 (11)	C11—H11B	0.9600
F4'—C2	1.405 (14)	C11—H11C	0.9600
F5'—C2	1.474 (13)	O1—C12	1.237 (9)
F6'—C2	1.313 (15)	O2—C12	1.290 (8)
N—C11	1.480 (7)	O2—H2A	0.8200
N—C9	1.523 (7)	O3—C14	1.394 (7)
N—H0A	0.8600	O3—H3A	0.8200
C1—C7	1.495 (11)	O4—C15	1.213 (7)
C2—C3	1.392 (13)	O5—C15	1.236 (7)
C3—C4	1.336 (9)	O5—H5A	0.8200
C3—C8	1.447 (11)	C12—C13	1.463 (9)
C4—C5	1.432 (10)	C13—C14	1.530 (8)
C4—H4A	0.9300	C13—H13A	0.9700
C5—C6	1.315 (9)	C13—H13B	0.9700
C5—C9	1.492 (8)	C14—C15	1.543 (8)
C6—C7	1.441 (10)	C14—H14A	0.9800
C6—H6A	0.9300
C11—N—C9	112.7 (5)	C5—C6—C7	121.6 (8)
C11—N—H0A	123.6	C5—C6—H6A	119.2
C9—N—H0A	123.6	C7—C6—H6A	119.2
F3'—C1—F2'	102.5 (11)	C8—C7—C6	119.4 (8)
F3'—C1—F1	128.3 (11)	C8—C7—C1	122.9 (8)
F2'—C1—F3	123.5 (10)	C6—C7—C1	117.6 (8)
F1—C1—F3	122.1 (10)	C7—C8—C3	120.8 (8)
F3'—C1—F1'	114.7 (11)	C7—C8—H8A	119.6
F2'—C1—F1'	94.2 (9)	C3—C8—H8A	119.6
F1—C1—F1'	56.8 (8)	C5—C9—C10	114.4 (5)
F3—C1—F1'	80.8 (8)	C5—C9—N	112.1 (5)
F3'—C1—C7	116.5 (10)	C10—C9—N	108.0 (5)
F2'—C1—C7	116.5 (9)	C5—C9—H9A	107.3
F1—C1—C7	113.2 (9)	C10—C9—H9A	107.3
F3—C1—C7	117.9 (7)	N—C9—H9A	107.3
F1'—C1—C7	110.3 (8)	C9—C10—H10A	109.5
F3'—C1—F2	59.7 (8)	C9—C10—H10B	109.5
F2'—C1—F2	56.9 (8)	H10A—C10—H10B	109.5
F1—C1—F2	96.9 (8)	C9—C10—H10C	109.5
F3—C1—F2	97.0 (8)	H10A—C10—H10C	109.5
F1'—C1—F2	144.0 (8)	H10B—C10—H10C	109.5
C7—C1—F2	102.4 (8)	N—C11—H11A	109.5
F5—C2—F6'	77.4 (9)	N—C11—H11B	109.5
F5—C2—C3	115.3 (9)	H11A—C11—H11B	109.5
F6'—C2—C3	130.1 (9)	N—C11—H11C	109.5
F5—C2—F4	106.1 (10)	H11A—C11—H11C	109.5
F6'—C2—F4	110.7 (10)	H11B—C11—H11C	109.5
C3—C2—F4	110.8 (10)	C12—O2—H2A	109.5
F5—C2—F6	103.2 (10)	C14—O3—H3A	109.5
C3—C2—F6	109.2 (9)	C15—O5—H5A	109.5
F4—C2—F6	112.1 (8)	O1—C12—O2	120.8 (7)
F5—C2—F4'	116.0 (10)	O1—C12—C13	121.8 (7)
F6'—C2—F4'	91.5 (9)	O2—C12—C13	117.4 (7)
C3—C2—F4'	119.0 (10)	C12—C13—C14	111.8 (5)
F6—C2—F4'	88.8 (8)	C12—C13—H13A	109.3
F6'—C2—F5'	104.7 (10)	C14—C13—H13A	109.3
C3—C2—F5'	107.4 (9)	C12—C13—H13B	109.3
F4—C2—F5'	81.7 (8)	C14—C13—H13B	109.3
F6—C2—F5'	132.1 (11)	H13A—C13—H13B	107.9
F4'—C2—F5'	99.5 (9)	O3—C14—C13	107.7 (4)
C4—C3—C2	124.2 (8)	O3—C14—C15	115.0 (5)
C4—C3—C8	118.5 (8)	C13—C14—C15	109.4 (5)
C2—C3—C8	116.8 (8)	O3—C14—H14A	108.2
C3—C4—C5	121.2 (7)	C13—C14—H14A	108.2
C3—C4—H4A	119.4	C15—C14—H14A	108.2
C5—C4—H4A	119.4	O4—C15—O5	126.3 (6)
C6—C5—C4	118.4 (7)	O4—C15—C14	117.3 (5)
C6—C5—C9	122.5 (7)	O5—C15—C14	116.3 (5)
C4—C5—C9	119.1 (6)
F5—C2—C3—C4	−8.6 (14)	F2—C1—C7—C8	63.3 (12)
F6'—C2—C3—C4	86.2 (14)	F3'—C1—C7—C6	−56.5 (14)
F4—C2—C3—C4	−129.1 (9)	F2'—C1—C7—C6	−177.7 (11)
F6—C2—C3—C4	107.0 (10)	F1—C1—C7—C6	138.1 (10)
F4'—C2—C3—C4	−153.3 (8)	F3—C1—C7—C6	−13.7 (14)
F5'—C2—C3—C4	−41.5 (11)	F1'—C1—C7—C6	76.5 (10)
F5—C2—C3—C8	179.6 (8)	F2—C1—C7—C6	−118.7 (8)
F6'—C2—C3—C8	−85.6 (13)	C6—C7—C8—C3	−0.6 (14)
F4—C2—C3—C8	59.1 (11)	C1—C7—C8—C3	177.4 (8)
F6—C2—C3—C8	−64.8 (10)	C4—C3—C8—C7	2.0 (13)
F4'—C2—C3—C8	34.8 (13)	C2—C3—C8—C7	174.3 (9)
F5'—C2—C3—C8	146.6 (8)	C6—C5—C9—C10	−128.2 (7)
C2—C3—C4—C5	−174.3 (8)	C4—C5—C9—C10	49.9 (8)
C8—C3—C4—C5	−2.6 (11)	C6—C5—C9—N	108.5 (7)
C3—C4—C5—C6	1.8 (11)	C4—C5—C9—N	−73.5 (7)
C3—C4—C5—C9	−176.3 (6)	C11—N—C9—C5	−66.8 (7)
C4—C5—C6—C7	−0.3 (11)	C11—N—C9—C10	166.3 (5)
C9—C5—C6—C7	177.8 (7)	O1—C12—C13—C14	−75.2 (9)
C5—C6—C7—C8	−0.3 (13)	O2—C12—C13—C14	103.5 (7)
C5—C6—C7—C1	−178.4 (8)	C12—C13—C14—O3	−55.0 (7)
F3'—C1—C7—C8	125.5 (13)	C12—C13—C14—C15	70.6 (7)
F2'—C1—C7—C8	4.3 (17)	O3—C14—C15—O4	−167.3 (5)
F1—C1—C7—C8	−39.9 (15)	C13—C14—C15—O4	71.4 (6)
F3—C1—C7—C8	168.3 (10)	O3—C14—C15—O5	9.4 (7)
F1'—C1—C7—C8	−101.5 (12)	C13—C14—C15—O5	−111.9 (6)

D—H···A	D—H	H···A	D···A	D—H···A
N—H0A···O4i	0.86	2.37	2.914 (7)	122
N—H0A···O3ii	0.86	2.20	2.887 (7)	137

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N—H0A⋯O4i	0.86	2.37	2.914 (7)	122
N—H0A⋯O3ii	0.86	2.20	2.887 (7)	137

Symmetry codes: (i) ; (ii) .