Acetic Acid → HCID 9822805, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-Chloro-5-(4-chlorophenyl)-3-(2-(S)-pyrrolidinylmethoxy)pyridine from step 150b above (270 mg, 0.75 mmol) in EtOH (5.0 mL) was added formalin (37%, 5 mL), sodium cyanoborohydride (240 mg, 3.75 mmol) and acetic acid (0.15 mL), and the mixture was stirred at 25° C. for 16 h. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with EtOAc, which was dried (MgSO4) and concentrated. (320 mg). The residue was converted to the salt by treatment with hydrogen chloride in Et2O/THF to afford the title compound (270 mg, 96%): mp 183-185° C.; 1H NMR (CD3OD) δ2.00-2.32 (m, 3H), 2.41 (m, 1H), 3.08 (s, 3H), 3.15 (m, 1H), 3.75 (m, 1H), 3.92 (m, 1H), 4.37 (dd, 1H, J=7.0, 11.0 Hz), 4.53 (dd, 1H, J=3, 11.0 Hz), 7.43-7.53 (m, 4H), 7.56 (d, 1H, J=4.5 Hz), 8.20 (d, 1H, J=3.0 Hz); MS (CI/NH3) m/z 337 (M+H)+. Anal. Calcd for C17H18Cl2N2O·1.3 HCl·0.1 H2O: C, 52.84; H, 5.09; N, 7.25. Found: C, 52.84; H, 4.84; N, 7.58. [α]25D -6.6 (c 0.42, MeOH).

Provenance & Evidence