反应详情

2-Fluoro-5-formylbenzonitrile (25 g, 167.6 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (450 mL) at RT. To this solution was added tert-butyl piperazine-1-carboxylate (31.2 g, 167.6 mmol, 1 equiv.) followed by the portion-wise addition of sodium triacetoxyborohydride (49.7 g, 234.6 mmol, 1.4 equiv.). The reaction vessel was placed under an atmosphere of nitrogen and allowed to stir at room temperature for 1 hour. Saturated NaHCO3 was added and the resultant mixture stirred for 10 minutes. The mixture was concentrated under reduced pressure, diluted with EtOAc (700 mL), and extracted into IN KHSO4 (3×150 mL). The aqueous layer was basified to pH 10 using 50% NaOH solution, saturated with NaCl, extracted into DCM (2×100 mL) and EtOAc (1×200 mL), and dried over Na2SO4. Concentration in vacuo resulted in the isolation of 10.2 g of tert-butyl 4-(3-cyano-4-fluorobenzyl)piperazine-1-carboxylate.

1. concentrationThe mixture was concentrated under reduced pressure
2. additiondiluted with EtOAc (700 mL)
3. extractionextracted into IN KHSO4 (3×150 mL)
4. extractionsaturated with NaCl, extracted into DCM (2×100 mL) and EtOAc (1×200 mL)
5. dry with materialdried over Na2SO4
6. concentrationConcentration in vacuo