Acetic Anhydride → HCID 59371301, compound

Participants

Reaction Steps

In a 15 mL round-bottom flask with magnetic stirrer, septum, and balloon (for pressure equalization and exclusion of moisture), neat acetic anhydride (23 μL, 0.24 mmol, 1.5 equiv.) was added with ice cooling in 5 min to a solution of 3-[5-[[1-(benzyloxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]benzylamine (65.3 mg, 162 μmol) and triethylamine (45 μL, 0.32 mmol, 2 equiv.) in anhydrous CH2Cl2 (1 mL). Stirring was continued at room temperature for 85 min, while the septum was replaced with a glass stopper to avoid evaporation losses. After 65 min, TLC (SiO2, CH2Cl2/MeOH 9:1, UV detection) demostrated complete conversion of the starting material (Rf approx. 0.05) to the acetamide (Rf approx. 0.45). Methanol (25 μL) was added, and the reaction mixture was stored at room temperature for 1 h before being directly applied on a SiO2 column (26×1.3 cm; eluent: CH2Cl2/MeOH 94:6 for a forerun, then 9:1). The product-containing fractions were evaporated and dried (50° C./oil pump) to yield 69.1 mg (96%) of the amide as a colorless glass. [α]D−40.7, [α]546−48.3 (c 14.8 g/L, EtOAc). 1H NMR (CDCl3, 500 MHz) δ 8.47 (s, 1H), 8.32 (br, 1H), 7.55-7.48 (m, 2H), 7.47 (t, 1H, J=7.5 Hz), approx. 7.4 (br and overlapping, 1H), 7.30 (d, 1H, J=7.4 Hz), 7.31 (br s, 5H), 5.89 (br, 1H), 5.12, 5.07 (ABq, 2H, J=12.3 Hz), 4.67 (br, 1H), 4.54 (d, 2H, J=5.7 Hz), approx. 4.4-4.5 (br, 1H), 4.22 (br, 1H), 4.09-4.00 (m, 2H), 2.51-2.32 (m, 2H), 2.08 (s, 3H). MS (EI) m/z 445 (M+, 8.46%), 354 (2.2%), 312 (2.8%), 310 (5.9%), 242 (6.5%), 199 (5.0%), 91 (100%), 43 (11%).

Provenance & Evidence