(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate → (3R)-1-(tert-butoxycarbonyl)-3-((3-fluorophenoxy)benzoyl)piperidine
Reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1)=[O:5].[F:20][C:21]1[CH:22]=[C:23]([CH:32]=[CH:33][CH:34]=1)[O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Li]>C1COCC1>[C:15]([O:14][C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@@H:6]([C:4](=[O:5])[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[O:24][C:23]2[CH:32]=[CH:33][CH:34]=[C:21]([F:20])[CH:22]=2)[CH2:7]1)=[O:13])([CH3:16])([CH3:17])[CH3:18]Participants
4
Procedure
To a solution of (R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate (0.65 g, 2.37 mmol) in THF (4 mL) at −20° C. was added dropwise the solution of 2-(3-fluorophenoxy)phenyllithium prepared in Step 2 above. After the addition was complete, the resulting solution was allowed to warm to rt slowly, and left at rt for 1 h. The reaction was quenched with 1N HCl (˜6 mL), and extracted with Et2O (4×10 mL). The combined organic layers were washed with satd aq NaHCO3 and brine, and dried over Na2SO4. Removal of the solvent left the crude ketone (1.49 g, quantitative), which was used for next step without further purification.