Reaction Steps
To a solution of 6-chloro-5-(5,5-dimethyl-1,3-hexadienyl)-3-(2-(S)-pyrrolidinylmethoxy)pyridine from Example 148a (150 mg, 0.38 mmol) in EtOH (3.0 mL) was added formalin (37%, 5 mL), sodium cyanoborohydride (120 mg, 1.9 mmol) and acetic acid (0.1 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 (MSO4) and concentrated. The residue was converted to the salt by treatment with hydrogen chloride in Et2O/THF to afford the title compound (143 mg, 100%): mp 220-220° C.; 1H NMR (CD3OD) δ1.10 (s, 9H), 2.08-2.18 (m, 2H), 2.23 (m, 1H), 2.41 (m, 1H), 3.08 (s, 3H), 3.23 (m, 1H), 3.75 (m, 1H), 3.92 (m, 1H), 4.35 (dd, 1H, J=5.5, 11.5 Hz), 4.53 (dd, 1H, J=3.5, 10.5 Hz), 6.05 (d, 1H, J=15.5 Hz), 6.28 (dd, 1H, J=9.5, 15.5 Hz), 6.73 (d, 1H, J=16.0 Hz), 7.00 (dd, 1H, J=10, 15.5 Hz), 7.75 (d, 1H, J=3.0 Hz), 8.00 (d, 1H, J=3.0 Hz); MS (CI/NH3) m/z 335 (M+H+), 669 (2M+H)+. Anal. Calcd for C19H27ClN2O·1.1 HCl·0.5 H2O: C, 59.43; H, 7.64; N, 7.30. Found: C, 59.55; H, 7.69; N, 7.36. [α]25D -4.5 (c 0.44, MeOH).
