4-(4-Chlorophenyl)piperidine

2.19.a Compound 42.4. 4-(4-Chlorophenyl)piperidine. Into a 250-mL round-bottom flask, was placed a solution of ter/-butyl 4-(4-chlorophenyl)piperidine-l -carboxylate (compound 42.3, 5.00 g, 16.9 mmol) in dichloromethane (100 mL), trifluoroacetic acid (9.6 g, 84 mmol). The resulting solution was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was carefully diluted with ethyl acetate (100 mL) and aqueous sodium bicarbonate was added until a pH of 8 was attained. The resulting mixture was washed with brine (100 mL) and the organic layer was dried (NaCompound 42.4. 4-(4-Chlorophenyl)piperidine. (i) Preparation of 4-(4-chlorophenyl) piperidine A solution of 4-(4-chlorophenyl)-1, 2, 5, 6-tetrahydropyridine (10.0 g, 52 mmol) in ethyl acetate (200 ml) containing 5% palladium on charcoal was hydrogenated at approximately 3 atmospheres until uptake of hydrogen ceased. The reaction was then filtered through 'Hyflo' (Trade Mark:diatomaceous earth) and evaporated in vacuo to give the desired product as an off-white solid (10.0 g, 99% yield), m.pt. 143 C. Low resolution mass spectroscopy revealed the mass/charge ratio of the parent molecule ion, M+, to be 195/197. Analysis: Calc. C:67.5; H:7.2; N:7.2%. Found C:66.5; H:8.2; N:6.9%.2.19.a 4-(4-chloro-phenyl)-piperidine To a solution of 5.0 g (21.7 mmol) of 4-(4-chloro-phenyl)-1, 2, 3, 6-tetrahydro-pyridine (cf. 2.13.a) in 20 mL methanol are added 500 mg Pd/C. The reaction mixture is stirred for 7 h at ambient temperature and 10 psi hydrogen. After separation of the catalyst the solvent is eliminated using the rotary evaporator. Further purification is carried out by column chromatography on silica gel (eluant: dichloromethane/methanol/ammonia=5:4.9:0.1). Yield: 3.2 (75.3% of theory); C11H14ClN (M=195.694); calc.: molar peak (M+H)+: 196/198 fnd.: molar peak (M+H)+: 196/198. Rf value: 0.37 (silica gel, dichloromethane/methanol/NH3 5:4.9:0.1).In an analogous manner, there are obtained from 3-phenylpyrrolidine; 4-(4-methoxyphenyl)piperidine; EXAMPLE 101 In the same manner as in Example 99 except that A solution of Intermediate'A' (200 mg, 0.55 mmol, 1.00 eq), 4-(4- chlorophenyl)piperidine (330 mg, 1.69 mmol, 3.00 eq), and Et3N (170 mg, 1.68 mmol, 3.00 eq) in CH2CI2 (3 mL) was stirred for 2 h at rt, then extracted with 2x20 mL of EtOAc. The combined organic layers were concentrated under vacuum and purified with silica gel chromatography using EtOAc / hexane (1:2) to afford 220 mg (89%) of the title compound as an off-white solid. LC-MS: (ES, m/z ): 446.

Molecular Weight:195.69
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:195.0814771
Monoisotopic Mass:195.0814771
Topological Polar Surface Area:12
Heavy Atom Count:13
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes