反应详情

To a solution of (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (7.09 g, 26.7 mmol) and (1S,2R)-ethyl 1-((diphenylmethylene)amino)-2-(methoxymethyl)cyclopropanecarboxylate (6 g, 17.78 mmol) in anhydrous THF (100 mL) was slowly (over 5 min) added a solution of potassium tert-butoxide (1 M in THF) at rt. The reaction was heated to 60° C. for approximately 20 h before acetic acid (10.68 g, 178 mmol) and absolute ethanol (20 mL) were added at 60° C. THF was distilled off, and the reaction was heated to reflux for 3 h. The reaction was cooled to rt before silica gel was added, and the solvent was removed under vacuum. The dry silica gel was packed and the product was purified by flash chromatography (EtOAc/hexane 1:19 to 6:14) to give (1S,2R)-5′-(4-chlorophenyl)-2-(methoxymethyl)-6′,7′-dimethylspiro[cyclopropane-1,3′-thieno[2,3-e][1,4]diazepin]-2′(1′H)-one a solid (3.7 g). LRMS (M+H)+: 375 m/z.

1. custom(over 5 min)
2. additionwere added at 60° C
3. distillationTHF was distilled off
4. temperaturethe reaction was heated
5. temperatureto reflux for 3 h
6. additionwas added
7. customthe solvent was removed under vacuum
8. customthe product was purified by flash chromatography (EtOAc/hexane 1:19 to 6:14)