反应详情

A mixture of 0.63 g (1.19 mmole) of (S)-4-(benzyloxycarbonyl)-1-[N-(3,5-dichlorophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid and 12 mL of 30% HBr/acetic acid was stirred at room temperature for 40 min, and residual HBr was then removed by bubbling nitrogen through the solution for 3 hr. The mixture was then concentrated in vacuo. The residue was treated with 25 mL of water and the pH adjusted to 7 with aqueous sodium hydroxide. To this mixture was added 45 mL of ethyl acetate, and the ethyl acetate layer was extracted with 5×25 mL of water. The combined water layers were treated with aqueous sodium hydroxide to adjust the pH to 7, and the aqueous was concentrated in vacuo to give 0.73 g of an oily solid, which was carried on immediately in Step F) below.

1. customresidual HBr was then removed
2. customby bubbling nitrogen through the solution for 3 hr
3. concentrationThe mixture was then concentrated in vacuo
4. additionThe residue was treated with 25 mL of water
5. additionTo this mixture was added 45 mL of ethyl acetate
6. extractionthe ethyl acetate layer was extracted with 5×25 mL of water
7. additionThe combined water layers were treated with aqueous sodium hydroxide
8. concentrationthe aqueous was concentrated in vacuo