反应详情

温度

60 °C

Sodium cyanoborohydride (8.57 mmol) was added to a solution of ethyl 6-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1,2-benzisothiazole-3-carboxylate (0.260 g, 0.857 mmol) and 1-ethoxy-1-(trimethylsilyloxy)cyclopropane (8.57 mmol) in ethanol (11.2 mL) and the reaction mixture was heated at 60° C. for 6 h. The reaction mixture was diluted with water (50 mL) and was extracted with ethyl acetate (2 ×50 mL). The combined organic layers were washed with brine (25 mL), dried (magnesium sulfate), and were concentrated. The residue was purified by chromatography (ethyl acetate) to yield the ester. A 5.0 M solution of sodium hydroxide in water (4.00 mL) was added to a solution of the ester in ethanol (10.0 mL) and the reaction mixture was maintained for 16 h. The reaction was neutralized with acetic acid and was loaded onto a SCX column. The column was flushed with water (200 mL) and methanol (100 mL) and the product was eluted with 2.0 M ammonia in methanol (60 mL) to provide the acid in 56% yield. The acid was used without further purification.

1. extractionwas extracted with ethyl acetate (2 ×50 mL)
2. washThe combined organic layers were washed with brine (25 mL)
3. dry with materialdried (magnesium sulfate)
4. concentrationwere concentrated
5. customThe residue was purified by chromatography (ethyl acetate)