Carbon Dioxide → HCID 59716450, compound

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyllithium in pentane (1.7 M, 42.5 mL, 72.3 mmol, 2.40 equiv) was added to a solution of tert-butyl thien-2-ylcarbamate (2-1, 6.00 g, 30.1 mmol, 1 equiv) in THF (300 mL) at −78° C. The reaction mixture was stirred for 45 min, then solid CO2 (approximately 20 g) was added and the resulting mixture was warmed to 0° C. and stirred for 30 minutes. The reaction mixture was partitioned between aqueous 1 N hydrochloric acid solution and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 100% ethyl acetate), and the polar fractions were concentrated. A solution of the residue, benzylamine (6.61 g, 61.7 mmol, 2.05 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.91 g, 30.8 mmol, 1.02 equiv), 1-hydroxy-7-azabenzotriazole (4.19 g, 30.8 mmol, 1.02 equiv), and triethylamine (8.59 mL, 61.7 mmol, 2.05 equiv) in DMF (100 mL) was stirred at 55° C. for 24 h. The reaction mixture was concentrated, and the residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (3×100 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column (hexanes initially, grading to 100% ethyl acetate) to give tert-butyl 3-[(benzylamino)carbonyl]thien-2-ylcarbamate (2-2) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.37 (m, 5H), 6.87 (d, 1H, J=5.8 Hz), 6.69 (d, 1H, J=5.8 Hz), 6.13 (s, 1H), 4.61 (d, 2H, J=5.5 Hz), 1.52 (s, 9H).

Provenance & Evidence