Tetrahydrofuran → 1-((S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-ol

HRID 338832Notes

Reaction equation

[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]=1

Participants

Reactant 4

HCID 8028Tetrahydrofuran

HCID 11430Potassium Carbonate

HCID 145784583-Methylpyrrolidin-3-ol

HCID 86707400(R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl trifluoromethanesulfonate

Product 1

HCID 867073991-((S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-3-methylpyrrolidin-3-olYield 54.6%

Conditions

Temperature: 50 °C

Procedure

A 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).

Workup

filtrationThe reaction was filtered
concentrationconcentrated under reduced pressure
customthe residue was purified by preparative HPLC (C18, 300 g, 10% MeCN/water to 95% MeCN/water over column volumes)

Sources & evidence

ORD record: ord-867849e8faab4345b9610fe3efe57960
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889704B2

Reaction notes

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