[CH:1]1([C@H:7]2[CH2:11][N:10](C(OC(C)(C)C)=O)[C@H:9]([C@H:19]([C:21]3[C:26]([Cl:27])=[CH:25][N:24]=[CH:23][C:22]=3[Cl:28])[OH:20])[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1CCCC1.[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35]>C(Cl)Cl>[F:37][C:36]([F:39])([F:38])[C:34]([OH:40])=[O:35].[CH:1]1([C@H:7]2[CH2:11][NH:10][C@H:9]([C@H:19]([C:21]3[C:26]([Cl:27])=[CH:25][N:24]=[CH:23][C:22]=3[Cl:28])[OH:20])[CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1(2S,4S)-tert-butyl 4-cyclohexyl-2-((S)-(3,5-dichloropyridin-4-yl)(hydroxy)methyl)pyrrolidine-1-carboxylate (1.20 g, 2.79 mmol) and its epimer at C2 of the pyrrolidine was treated with DCM (10 mL) and TFA (7 mL, 91 mmol) and allowed to stir at room temperature for 1.5 h. The reaction mixture was concentrated on the rotovap and the crude residue purified on an ISCO Combiflash™ RF (40 g Grace Reveleris column, using a gradient of 0-20% 2M NH3/MeOH in DCM) affording (S)-((2S,4S)-4-cyclohexylpyrrolidin-2-yl)(3,5-dichloropyridin-4-yl)methanol 2,2,2-trifluoroacetate (755 mg, 1.705 mmol, 61% yield) along with its epimer at C2 of the pyrrolidine as a light tan-colored foam. MS (ESI) 329.0, 331.1 [M+H]+.
Wird geladen…