3-Boc-1,2,3-oxathiazolidine 2,2-dioxide → HCID 68183265, compound

Participants

Reaction Conditions

Reaction Steps

Glasswares were flame-dried before use. A solution of ethyl 3-(4-chlorobenzyl)-5-morpholin-4-ylthiophene-2-carboxylate (0.872 g, 2.38 mmol) in N,N-dimethylformamide (16.0 mL) and tetrahydrofuran (4.00 mL) was cooled to −78° C. with vigorous stirring. The solution was evacuated under highvac and purged with argon (×4). 1.00 M Sodium hexamethyldisilazane in tetrahydrofuran (2.62 mL, 2.62 mmol) was added; the solution turned deep purple. The mixture was stirred at −78° C. under argon for 10 min. A solution of tert-butyl 1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (1.06 g, 4.77 mmol) in N,N-dimethylformamide (4.00 mL) was added dropwise over −1 min. The solution turned light red, and then slightly dark green in −1 min. In 15 min, the reaction was warmed to 0° C., and then in 1 h, it was warmed to rt. After 15 min of stirring at rt, the reaction was quenched and distributed between NH4Cl saturated solution and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined organic layer was washed with 10% LiCl aqueous solution (×2) and brine, dried, and concentrated. Purification on a silica gel column (continuous gradient from 5% EtOAc/hexanes to 25% EtOAc/hexanes over 30 min) provided 776 mg of ethyl 3-{3-[(tert-butoxycarbonyl)amino]-1-(4-chlorophenyl)propyl}-5-(morpholin-4-yl)thiophene-2-carboxylate (64% yield) and 303 mg of unreacted ethyl 3-(4-chlorobenzyl)-5-morpholin-4-ylthiophene-2-carboxylate (35% yield). LCMS: (AA) ES+ 510, 512; 1H NMR (400 MHz, CDCl3) δ 7.24-7.21 (s, 4H), 5.88-5.82 (s, 1H), 5.21-5.11 (t, J=7.8 Hz, 1H), 5.06-4.94 (s, 1H), 4.34-4.22 (qd, J=7.1, 2.8 Hz, 2H), 3.83-3.73 (t, J=4.9 Hz, 4H), 3.29-3.19 (s, 1H), 3.22-3.12 (t, J=4.9 Hz, 4H), 2.99-2.85 (m, 1H), 2.25-2.12 (d, J=6.6 Hz, 1H), 2.12-2.06 (s, 1H), 1.47-1.41 (s, 9H), 1.36-1.31 (m, 3H).

Provenance & Evidence