Trifluoroacetic acid → (R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine
Reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2C(OC(C)(C)C)=O)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1>C(Cl)Cl>[F:8][C:9]1[CH:10]=[C:11]([C@H:17]2[CH2:21][CH2:20][CH2:19][NH:18]2)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1Participants
4
Procedure
A DCM (12 mL) solution of TFA (11.3 mL, 146 mmol) was added to (R)-tert-butyl 2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidine-1-carboxylate (4.33 g, 14.6 mmol) and stirred at ambient temperature for 1 hour. The reaction was then concentrated, taken up in EtOAc, then washed with NaHCO3 and brine. The organic phase was dried (MgSO4), filtered, and concentrated, and the crude material was purified by silica column chromatography eluting with a 1-2% 7 N NH3-MeOH/DCM to afford (R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine as a liquid (1.40 g, 49% yield).