反应详情

A 50% solution of propane phosphonic acid anhydride (0.964 g) (T3P) in DMF was added to a stirred solution of (S)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (0.290 g), (S)-4′-(2-amino-2-cyanoethyl)-3-fluorobiphenyl-4-carbonitrile (0.335 g) and triethylamine (0.880 mL) in DMF (3 mL) at 0° C. The resulting solution was allowed to warm to RT and stirred for 18 h. The mixture was poured into water and brine and the mixture extracted with ethyl acetate. The organics were washed with saturated brine, dried and evaporated. The crude product was purified by flash silica chromatography, eluting with 30% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford (S)-tert-butyl 2-((S)-1-cyano-2-(4′-cyano-3′-fluorobiphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylate as a colourless solid (0.443 g).

1. extractionthe mixture extracted with ethyl acetate
2. washThe organics were washed with saturated brine
3. customdried
4. customevaporated
5. customThe crude product was purified by flash silica chromatography
6. washeluting with 30% ethyl acetate in isohexane
7. customPure fractions were evaporated to dryness