[CH3:1][C:2]1([OH:7])[CH2:6][CH2:5][NH:4][CH2:3]1.FC(F)(F)S(O[C@H:14]([C:19]1[CH:20]=[N:21][C:22]([Cl:25])=[CH:23][CH:24]=1)[C:15]([F:18])([F:17])[F:16])(=O)=O.C([O-])([O-])=O.[K+].[K+].C1COCC1>>[Cl:25][C:22]1[N:21]=[CH:20][C:19]([C@H:14]([N:4]2[CH2:5][CH2:6][C:2]([CH3:1])([OH:7])[CH2:3]2)[C:15]([F:18])([F:16])[F:17])=[CH:24][CH:23]=1A mixture of 3-methylpyrrolidin-3-ol (1.41 g, 13.9 mmol), (R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl trifluoromethanesulfonate (4.30 g, 12.5 mmol) and K2CO3 (1.93 g, 13.9 mmol) in THF (69.7 mL, 13.9 mmol) was heated in a sealed tube to 50° C. overnight. The reaction was filtered, concentrated under reduced pressure and the residue was purified by preparative HPLC (C18, 300 g, 10% MeCN/water to 95% MeCN/water over column volumes) to give 1-((S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-ol (2.01 g, 48.9% yield).
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