Reaction Steps
To 5-(5,5-dimethyl-1,3-hexadienyl)-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 77a (145 mg, 0.34 mmol) was added formalin (37%, 4 mL) and formic acid (2 mL), and the mixture was heated at 70° C. for 3 hours. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2:MeOH 100:4 to afford to give the free base of the title compound (72.5 mg, 66% yield). MS (CI/NH3) m/z 335 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.10 (s, 9H), 1.77 (m, 2H), 2.00 (m, 1H), 2.28 (m, 1H), 2.45 (m, 3H), 2.70 (m, 1H), 3.10 (m, 1H), 3.43 (m, 1H), 4.00 (m, 1H), 4.38 (m, 1H), 5.95 (m, 1H), 6.20 (m, 1H), 6.70 (m, 2H), 7.38 (m, 1H), 7.93 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in Et2O/THF to give the title compound. mp 194° C. (dec). MS (CI/NH3) m/z 335 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 1.07 (s, 9H), 1.78-2.05 (m, 2H) 2.17-2.28 (m, 1H), 2.90 (dd, J=5.1, 31.9 Hz, 3H), 3.12 (m, 1H), 3.50 (m, 3H), 4.41 (m, 2H), 6.04 (d, J=15.6 Hz, 1H), 6.30 (dd, J=10.2, 15.2 Hz, 1H), 6.70 (d, J-15.6 Hz, 1H), 7.10 (ss, J=10.2, 15.6 Hz, 1H), 7,.84 (d, J=3.0 Hz, 1H), 8.06 (d, J=3.1 Hz, 1H). Anal. Calcd for C19H27N2OCl.1.7 HCl.0.8 Et2O: C, 58.45; H, 8.11; N, 6.14. Found: C, 58.58; H, 8.11; N, 5.85. [α]25D=+6.95° (c 0.71, MeOH).
