Sodium Methoxide → HCID 68613216, compound

Participants

Reaction Steps

To a solution of (1S,2S)-2-[5-[[1-(tert-butoxycarbonyl)-(2S)-azetidinyl]methoxy]-3-pyridyl]cyclopropylmethyl isobutyrate (2.82 g, 6.97 mmol) in anhydrous methanol (35 mL) in a 250 mL round-bottom flask with magnetic stirrer was added a 25-30 wt % solution of sodium methoxide in methanol (0.4 mL; d 0.97 kg/L according to supplier, which makes approx. 2 mmol). The flask was fitted with an Ar balloon, the atmosphere was exchanged, and the reaction mixture was kept at 40° C. for 6 h. The reaction mixture was evaporated and the residue directly filtered over silica gel (24×3.8 cm, CH2Cl2/MeOH 93:7, then 9:1). Evaporation and drying (50° C./oil pump) gave 2.29 g (98%) of a slightly yellowish glass. 1H NMR (CDCl3, TMS, 400 MHz) δ 8.13 (d, 1H, J=2.8 Hz), 8.04 (narrow m, 1H), 6.89 (m, 1H), 4.50 (m, 1H), 4.29 (m, 1H), 4.12 (m, 1H; the main structure of this signal is a dd with J=2.8 and 10.1 Hz, accompanied by minor peaks that may result from the presence of a second rotamer), 3.93-3.85 (m, 2H), 3.68, 3.62 (ABq, 2H, J=11.4 Hz, low-field part d with J=6.4 Hz, high-field part d with J=6.9 Hz), 2.40-2.22 (m, 2H), 1.83 (m, 1H), 1.70 (very br, 1H, OH), 1.48 (m, 1H), 1.42 (s, 9H), 1.03-0.97 (m, 2H). MS (EI) m/z 334 (M+, 1.0%), 278 (M+-C4H8, 2.4%), 237 (10%), 178 (19%), 100 (21%), 57 (100%), 56 (76%), 41 (44%).

Provenance & Evidence