(R)-(−)-Quinuclidin-3-ol

Rousselin, Y.; Clavel, A.; Bonnaventure, I.

doi:10.1107/S1600536813026998

organic compounds

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ISSN: 2056-9890

Volume 69| Part 11| November 2013| Page o1672

doi:10.1107/S1600536813026998

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(R)-(−)-Quinuclidin-3-ol

Yoann Rousselin,^a ^* Alexandre Clavel ^b and Isabelle Bonnaventure ^b

^aInstitut de Chimie Moleculaire de l'Universite de Bourgogne - ICMUB, UMR CNRS 6302, Universite de Bourgogne, 9, Av. Alain Savary, 21078 Dijon Cedex, France, and ^bCordenPharma – Synkem, 47 rue de Longvic, 21301 Chenove, France
^*Correspondence e-mail: yoann.rousselin@u-bourgogne.fr

(Received 6 September 2013; accepted 1 October 2013; online 19 October 2013)

The structure of the title compound [alternatively called (R)-(−)-1-azabicyclo[2.2.2]octan-3-ol], C₇H₁₃NO, at 100 K has hexagonal (P6₁) symmetry. The structure shows a twist along the C—N pseudo-threefold axis. In the crystal, molecules are linked via O—H⋯N hydrogen bonds, forming infinite chains along the c-axis direction. The crystal studied was twinned by merohedry (twin law: 010, 100, 00-1; population: 0.925:0.075)

CCDC reference: 963962

Related literature

The title compound is a key building block for the syntheses of muscarinic receptor ligands, including solifenacin (Naito et al., 2005 ), revatropate (Alabaster, 1997 ) and talsaclidine (Leusch et al., 2000 ). For properties of the title compound, see: Bosak et al. (2005 ); Carroll et al. (1991 ); Frackenpohl & Hoffmann (2000 ); Day & Motherwell (2006 ); Malone & Armstrong (2006 ); Siczek & Lis (2008 ); Sterling et al. (1988 ). For puckering parameters, see: Cremer & Pople (1975 ); For absolute configuration, see: Flack (1983 ); The twin law was determined using TwinRotMat implemented in PLATON (Spek, 2009 ).

Experimental

Crystal data

C₇H₁₃NO
M_r = 127.18
Hexagonal, P 6₁
a = 6.2076 (3) Å
c = 29.8731 (13) Å
V = 996.91 (11) Å³
Z = 6
Cu Kα₁ radiation
μ = 0.67 mm⁻¹
T = 100 K
0.58 × 0.44 × 0.32 mm

Data collection

Bruker D8 VENTURE diffractometer
Absorption correction: numerical (SADABS; Bruker, 2012 ) T_min = 0.58, T_max = 0.74
15447 measured reflections
1240 independent reflections
1240 reflections with I > 2σ(I)
R_int = 0.026

Refinement

R[F² > 2σ(F²)] = 0.023
wR(F²) = 0.064
S = 1.15
1240 reflections
85 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.12 e Å⁻³
Absolute structure: Parsons & Flack (2004 ).
Absolute structure parameter: 0.01 (4)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N1ⁱ	0.84	2.00	2.8366 (19)	176
Symmetry code: (i) $[y-1, -x+y, z-{\script{1\over 6}}]$ .

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

CCDC reference: 963962

Crystal structure: contains datablock I. DOI: 10.1107/S1600536813026998/bg2517sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813026998/bg2517Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813026998/bg2517Isup3.cml

checkCIF report

Comment top

(R)-(-)-quinuclidin-3-ol (Figure 1) is a key building block for the syntheses of muscarinic receptor ligands, including solifenacin (M3 receptor antagonist),(Naito et al., 2005) revatropate (M3 receptor antagonist),(Alabaster, 1997) and talsaclidine (M1 receptor agonist),(Leusch et al., 2000).

The asymetric unit of the crystal (Figure 1) consists of one single (R)-(-)-quinuclidin-3-ol molecule.

The quinuclidinol moiety has pseudo-threefold symmetry about the N1-C3 axis with C6-N1-C1, C1-N1-C5 and C5-N1-N6 angles of 108.86 (15)°, 108.73 (14)° and 108.72 (14)° respectively, and N1-C1-C2-C3, N1-C6-C7-C3 and N1-C5-C4-C3 torsion angles of -0.9 (3)°, 0.4 (2)° and 0.2 (2)° respectively.

The three piperidine rings formed by (N1, C1, C2, C3, C4, C5), (N1, C5, C4, C3, C7, C6) and (N1, C6, C7, C3, C2, C1) adopt a boat conformation with total puckering amplitutdes QT of 0.8218 (0) (with Θ = 91.84 (0)° and ϕ = -0.2 (0)°), QT of 0.8141 (1) (with Θ = 91.55 (0)° and ϕ = 0.19 (0)°) and QT of 0.8123 (0) (with Θ = 90.95 (0)° and ϕ = -0.17 (0)°), respectively (Cremer & Pople, (1975)).

There is a hydrogen bond (Table 1) which links molecules into infinite chains along the c axis (Figure 2).

Related literature top

The title compound is a key building block for the syntheses of muscarinic receptor ligands, including solifenacin (Naito et al., 2005), revatropate (Alabaster, 1997) and talsaclidine (Leusch et al., 2000). For properties of the title compound, see: Bosak et al. (2005); Carroll et al. (1991); Frackenpohl & Hoffmann (2000); Day & Motherwell (2006); Malone & Armstrong (2006); Siczek & Lis (2008); Sterling et al. (1988). For puckering parameters, see: Cremer & Pople (1975); For absolute configuration, see: Flack (1983); The twin law was determined using TwinRotMat implemented in PLATON (Spek, 2009).

Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

	Fig. 1. A view of (R)-(-)-quinuclidin-3-ol with atom labelling scheme. The thermal displacement ellipsoids are drawn at 50% probability level.
	Fig. 2. A view of molecular packing showing chains running along the c direction. The hydrogen bonds are shown as dashed lines. The thermal displacement ellipsoids are drawn at 50% probability level.

(R)-(-)-Quinuclidin-3-ol top

Crystal data top

C₇H₁₃NO	D_x = 1.271 Mg m⁻³
M_r = 127.18	Melting point: 492(2) K
Hexagonal, P6₁	Cu Kα₁ radiation, λ = 1.54178 Å
a = 6.2076 (3) Å	µ = 0.67 mm⁻¹
c = 29.8731 (13) Å	T = 100 K
V = 996.91 (11) Å³	Prism, clear light colourless
Z = 6	0.58 × 0.44 × 0.32 mm
F(000) = 420

Data collection top

Bruker D8 VENTURE diffractometer	1240 independent reflections
Radiation source: sealed X-ray tube, high brilliance microfocus sealed tube, Cu	1240 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.026
Detector resolution: 1024 x 1024 pixels mm^-1	θ_max = 69.2°, θ_min = 4.4°
ϕ and ω scans	h = −7→7
Absorption correction: numerical (SADABS; Bruker, 2012)	k = −7→7
T_min = 0.58, T_max = 0.74	l = −34→35
15447 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.023	w = 1/[σ²(F_o²) + (0.0394P)² + 0.1183P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.064	(Δ/σ)_max < 0.001
S = 1.15	Δρ_max = 0.23 e Å⁻³
1240 reflections	Δρ_min = −0.12 e Å⁻³
85 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.0156 (15)
0 constraints	Absolute structure: Parsons & Flack (2004).
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.01 (4)

Crystal data top

C₇H₁₃NO	Z = 6
M_r = 127.18	Cu Kα₁ radiation
Hexagonal, P6₁	µ = 0.67 mm⁻¹
a = 6.2076 (3) Å	T = 100 K
c = 29.8731 (13) Å	0.58 × 0.44 × 0.32 mm
V = 996.91 (11) Å³

Data collection top

Bruker D8 VENTURE diffractometer	1240 independent reflections
Absorption correction: numerical (SADABS; Bruker, 2012)	1240 reflections with I > 2σ(I)
T_min = 0.58, T_max = 0.74	R_int = 0.026
15447 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.023	H-atom parameters constrained
wR(F²) = 0.064	Δρ_max = 0.23 e Å⁻³
S = 1.15	Δρ_min = −0.12 e Å⁻³
1240 reflections	Absolute structure: Parsons & Flack (2004).
85 parameters	Absolute structure parameter: 0.01 (4)
1 restraint

Special details top

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. Refined as a 2-component twin.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	−0.1928 (2)	0.4528 (2)	0.48963 (4)	0.0175 (3)
H1	−0.2253	0.4264	0.4622	0.026*
N1	0.3057 (3)	0.6832 (3)	0.56404 (5)	0.0157 (4)
C2	0.5095 (3)	0.8018 (3)	0.48879 (6)	0.0166 (4)
H2A	0.5325	0.9500	0.4722	0.020*
H2B	0.6378	0.7625	0.4786	0.020*
C4	0.0565 (3)	0.6495 (3)	0.49520 (5)	0.0149 (4)
H4	0.0812	0.7999	0.4785	0.018*
C1	0.5354 (4)	0.8550 (4)	0.53973 (6)	0.0208 (4)
H1A	0.6752	0.8380	0.5515	0.025*
H1B	0.5744	1.0283	0.5450	0.025*
C7	0.2139 (3)	0.3542 (3)	0.50634 (5)	0.0159 (4)
H7A	0.3369	0.3067	0.4966	0.019*
H7B	0.0450	0.2111	0.5013	0.019*
C5	0.0986 (4)	0.7091 (4)	0.54597 (5)	0.0188 (4)
H5A	0.1340	0.8814	0.5510	0.023*
H5B	−0.0557	0.5956	0.5624	0.023*
C3	0.2487 (3)	0.5801 (3)	0.47977 (6)	0.0141 (4)
H3	0.2279	0.5406	0.4471	0.017*
C6	0.2509 (4)	0.4253 (4)	0.55649 (6)	0.0204 (4)
H6A	0.0984	0.3095	0.5732	0.024*
H6B	0.3897	0.4068	0.5684	0.024*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0134 (6)	0.0222 (6)	0.0150 (6)	0.0076 (5)	−0.0012 (4)	−0.0004 (5)
N1	0.0176 (7)	0.0155 (8)	0.0128 (7)	0.0074 (6)	−0.0005 (6)	−0.0014 (5)
C2	0.0149 (8)	0.0186 (9)	0.0145 (8)	0.0069 (7)	0.0009 (7)	0.0010 (6)
C4	0.0150 (8)	0.0161 (8)	0.0138 (8)	0.0079 (7)	−0.0002 (6)	0.0006 (7)
C1	0.0176 (9)	0.0215 (9)	0.0164 (9)	0.0045 (8)	−0.0020 (6)	−0.0034 (7)
C7	0.0150 (8)	0.0151 (8)	0.0177 (8)	0.0077 (7)	−0.0012 (6)	−0.0028 (7)
C5	0.0207 (9)	0.0237 (9)	0.0153 (8)	0.0135 (8)	−0.0006 (7)	−0.0042 (7)
C3	0.0135 (8)	0.0158 (8)	0.0124 (8)	0.0068 (7)	−0.0011 (6)	−0.0024 (7)
C6	0.0292 (9)	0.0186 (9)	0.0159 (9)	0.0139 (8)	−0.0003 (8)	0.0013 (7)

Geometric parameters (Å, º) top

O1—H1	0.8400	C1—H1A	0.9900
O1—C4	1.423 (2)	C1—H1B	0.9900
N1—C1	1.475 (2)	C7—H7A	0.9900
N1—C5	1.475 (2)	C7—H7B	0.9900
N1—C6	1.479 (2)	C7—C3	1.530 (2)
C2—H2A	0.9900	C7—C6	1.546 (2)
C2—H2B	0.9900	C5—H5A	0.9900
C2—C1	1.548 (2)	C5—H5B	0.9900
C2—C3	1.536 (2)	C3—H3	1.0000
C4—H4	1.0000	C6—H6A	0.9900
C4—C5	1.552 (2)	C6—H6B	0.9900
C4—C3	1.528 (2)

C4—O1—H1	109.5	C3—C7—H7A	110.1
C1—N1—C6	108.86 (15)	C3—C7—H7B	110.1
C5—N1—C1	108.73 (14)	C3—C7—C6	107.96 (13)
C5—N1—C6	108.72 (14)	C6—C7—H7A	110.1
H2A—C2—H2B	108.4	C6—C7—H7B	110.1
C1—C2—H2A	110.0	N1—C5—C4	112.56 (14)
C1—C2—H2B	110.0	N1—C5—H5A	109.1
C3—C2—H2A	110.0	N1—C5—H5B	109.1
C3—C2—H2B	110.0	C4—C5—H5A	109.1
C3—C2—C1	108.29 (15)	C4—C5—H5B	109.1
O1—C4—H4	109.6	H5A—C5—H5B	107.8
O1—C4—C5	107.46 (13)	C2—C3—H3	109.9
O1—C4—C3	112.96 (14)	C4—C3—C2	108.41 (14)
C5—C4—H4	109.6	C4—C3—C7	109.25 (14)
C3—C4—H4	109.6	C4—C3—H3	109.9
C3—C4—C5	107.45 (13)	C7—C3—C2	109.45 (14)
N1—C1—C2	111.72 (14)	C7—C3—H3	109.9
N1—C1—H1A	109.3	N1—C6—C7	112.19 (14)
N1—C1—H1B	109.3	N1—C6—H6A	109.2
C2—C1—H1A	109.3	N1—C6—H6B	109.2
C2—C1—H1B	109.3	C7—C6—H6A	109.2
H1A—C1—H1B	107.9	C7—C6—H6B	109.2
H7A—C7—H7B	108.4	H6A—C6—H6B	107.9

O1—C4—C5—N1	122.04 (17)	C5—C4—C3—C2	−59.75 (17)
O1—C4—C3—C2	−178.09 (13)	C5—C4—C3—C7	59.46 (17)
O1—C4—C3—C7	−58.88 (17)	C3—C2—C1—N1	−0.9 (2)
C1—N1—C5—C4	59.38 (18)	C3—C4—C5—N1	0.20 (19)
C1—N1—C6—C7	−59.78 (19)	C3—C7—C6—N1	0.4 (2)
C1—C2—C3—C4	60.54 (19)	C6—N1—C1—C2	59.72 (19)
C1—C2—C3—C7	−58.55 (18)	C6—N1—C5—C4	−59.01 (19)
C5—N1—C1—C2	−58.6 (2)	C6—C7—C3—C2	58.56 (18)
C5—N1—C6—C7	58.53 (19)	C6—C7—C3—C4	−60.01 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1ⁱ	0.84	2.00	2.8366 (19)	176

Symmetry code: (i) y−1, −x+y, z−1/6.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1ⁱ	0.84	2.00	2.8366 (19)	175.7

Symmetry code: (i) y−1, −x+y, z−1/6.

Acknowledgements

We thank Ms Marie-Jose Penouilh for the NMR and ESI mass spectra.

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