反应详情

温度

0 °C

To a stirred solution of 2-chloro-6-fluorobenzyl magnesium chloride (12.8 mL, 3.20 mmol, 3 equiv., available from Rieke Metals) in anhydrous tetrahydrofuran (15 ml) at 0° C. under nitrogen was added a solution of (4-Benzyl-morpholin-2-yl)-phenyl-methanone (300 mg, 1.07 mmol, 1 equiv.) in tetrahydrofuran (5 ml) dropwise over 15 minutes. The reaction was then stirred at 0° C. for one hour. The reaction mixture was allowed to warn to room temperature over two hours and stirred for a further 18 h. The solvent was then evaporated “in vacuo” and the residue redissolved in dichloromethane (30 mL). The organic solution was washed with aqueous saturated solution of NaHCO3 (50 mL). The aqueous solution was extracted with dichloromethane using a hydrophobic phase separator. The dichloromethane was evaporated “in vacuo” and redissolved in methanol (2 mL). The sample was bound to SCX-2 (5 g) and washed with methanol (30 mL). The sample was eluted using 2M ammonia in methanol (30 mL). The solvent was then evaporated using a reacti-therm blow down station to give 450 mg of a yellow amorphous solid. This material was used in step b) without further purification. LCMS (6 minutes method) [M+H]+=426 @ Rt 3.27 min. major peak.

1. waitto warn to room temperature over two hours
2. stirringstirred for a further 18 h
3. customThe solvent was then evaporated “in vacuo”
4. dissolutionthe residue redissolved in dichloromethane (30 mL)
5. washThe organic solution was washed with aqueous saturated solution of NaHCO3 (50 mL)
6. extractionThe aqueous solution was extracted with dichloromethane using a hydrophobic phase separator
7. customThe dichloromethane was evaporated “in vacuo”
8. dissolutionredissolved in methanol (2 mL)
9. washwashed with methanol (30 mL)
10. washThe sample was eluted
11. customThe solvent was then evaporated