Lithium tri-s-butylborohydride → (3R,4S)-Benzyl 3-fluoro-4-hydroxypiperidine-1-carboxylate
Reaction equation
CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[F:15][CH:16]1[C:21](=[O:22])[CH2:20][CH2:19][N:18]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:17]1>C1COCC1>[F:15][C@H:16]1[C@@H:21]([OH:22])[CH2:20][CH2:19][N:18]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:17]1Participants
4
Procedure
L-Selectride® (663 mL, 663 mmol) was added dropwise to an ice cold solution of benzyl 3-fluoro-4-oxopiperidine-1-carboxylate (138.9 g, 552.8 mmol) dissolved in anhydrous THF (421 mL). The ice bath was removed and the reaction was allowed to stand for 12 hours. The reaction mixture was carefully added (dropwise, via addition funnel) to a vigorously stirring mixture of 80 mL MeOH, 2 N NaOH (1400 mL) H2O2 (376 mL, 50%) in a large amount of ice, taking care to control the temperature rise. The mixture was stirred for 12 hours, then 2 L of EtOAc was added. The mixture was stirred an additional 1 hour. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to an oil (112 g). The residue was purified by flash column chromatography (silica gel, eluting with a gradient of 30% EtOAc to 75% EtOAc in hexanes) to afford 38 g of the desired compound.