反应详情

温度

0 °C

The tert-butyl 4-(3-cyano-4-fluorobenzyl)piperazine-1-carboxylate from the previous step (15.0 g, 47.0 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (150 mL), to which TFA (150 mL) was slowly added and the resultant mixture stirred for 10 minutes. CH2Cl2 and TFA were removed by concentration in vacuo. The resulting residue was dissolved in THF (170 mL) and Et3N (Aldrich, redistilled, 16.6 mL, 188.1 mmol, 4.0 equiv.). The reaction vessel was cooled to 0° C. and ethyl chloroformate (Aldrich, 4.7 mL, 49.4 mmol, 1.05 equiv.) was added dropwise via syringe under a nitrogen atmosphere. After 30 minutes the reaction was concentrated under reduced pressure, diluted with EtOAc, washed with sat. aq. NaHCO3 and brine, and dried over Na2SO4. The organic layer was removed in vacuo to yield 5.9 g of ethyl 4-(3-cyano-4-fluorobenzyl)piperazine-1-carboxylate.

1. additionwas slowly added
2. customCH2Cl2 and TFA were removed by concentration in vacuo
3. dissolutionThe resulting residue was dissolved in THF (170 mL)
4. concentrationAfter 30 minutes the reaction was concentrated under reduced pressure
5. additiondiluted with EtOAc
6. washwashed with sat. aq. NaHCO3 and brine
7. dry with materialdried over Na2SO4
8. customThe organic layer was removed in vacuo