Reaction Steps
A suspension of 5% Pt on carbon and 2-chloro-3-vinyl-5-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine (Example 26 above, 440 mg, 1.36 mmol) in MeOH (10 mL) were stirred overnight under an atmosphere of hydrogen (balloon). The mixture was filtered and the filtrate was concentrated to afford 2-chloro-3-ethyl-5-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine as a colorless oil (219 mg, 51%): 1H NMR (CDCl3, 300 MHz) δ 1.25 (t, J=7.5 Hz, 3H), 1.42 (s, 9H), 2.32 (m, 2H), 2.71 (q, J=7.5 Hz, 2H), 3.89 (t, J=7.8 Hz, 2H), 4.12 (dd, J=3.0, 9.8 Hz, 1H), 4.30 (m, 1H), 4.50 (m, 1H), 7.16 (d, J=3.1 Hz, 1H), 7.94 (d, J=3.0 Hz, 1H); MS (CI/NH3) m/z 327 (M+H)+. To a solution of the product from above (216 mg, 0.66 mmol) in CH2Cl2 (2 mL) at 0° C. was added trifluoroacetic acid (1.8 miL). The solution was allowed to warm to room temperature, then adjusted to pH 11 with aqueous 10% NaOH, and extracted with CH2Cl2. The organic extract was dried over MgSO4 and concentrated. The residue was chromatographed (silica gel; CH2Cl2 /MeOH, 100:3 to 100:15) to afford the free base of the title compound as an oil (60 mg, 40%): 1H NMR (CDCl3, 300 MHz) δ 1.22 (m 3H), 2.38 (m, 2H), 2.71 (q, J=7.5 Hz, 2H), 3.57 (m, 1H), 3.80 (m, 1H), 4.08 (m, 2H), 4.38 (m, 1H), 7.15 (d, J=2.4 Hz, 1H), 7.92 (d, J=3.0 Hz, 1H); MS (CI/NH3) m/z: 227 (M+H)+. The free base was dissolved in THF and treated with 1 M HCl in Et2O to afford the hydrochloride salt, which was triturated with Et2O and dried under vacuum to afford the title compound as a white solid: mp 102-104° C.; [α]D23 -9.68 (c 0.62, MeOH); 1H NMR (D2O) δ 1.24 (t, J=7.5 Hz, 3H), 2.71 (m, 4H), 4.11 (m, 2H), 4.42 (d, J=4 Hz, 2H), 4.95 (m, 1H), 7.51 (d, J=3 Hz, 1H), 8.00 (d, J=3 Hz, 1H). Anal. Calcd. for C11H15N2OCl.1.1 HCl: C, 49.52; H, 6.08; N, 10.50. Found: C, 49.63; H, 5.89; N, 10.20.
