Trifluoroacetic acid water → (R)-3-(2-(((R)-1-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino) pyrimidin-4-yl)-4-(1-hydroxyethyl)oxazolidin-2-one

HRID 57489Notes

Reaction equation

HRID 57489 reaction equation
C([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH:21]([C:23]2[O:27][N:26]=[C:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[C:30]([Cl:39])[CH:29]=3)[N:24]=2)[CH3:22])[N:15]=1)[CH3:7])(C)(C)C.C(O)(C(F)(F)F)=O.O>>[Cl:39][C:30]1[CH:29]=[C:28]([C:25]2[N:24]=[C:23]([C@H:21]([NH:20][C:16]3[N:15]=[C:14]([N:9]4[C@@H:8]([CH:6]([OH:5])[CH3:7])[CH2:12][O:11][C:10]4=[O:13])[CH:19]=[CH:18][N:17]=3)[CH3:22])[O:27][N:26]=2)[CH:33]=[CH:32][C:31]=1[O:34][C:35]([F:36])([F:38])[F:37]

Participants

3

Reactant 2

HCID 22392675Trifluoroacetic acid waterHCID 90414497HCID 90414497, compound

Product 1

HCID 90414569(R)-3-(2-(((R)-1-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino) pyrimidin-4-yl)-4-(1-hydroxyethyl)oxazolidin-2-oneYield 66.3%

Procedure

(4R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-((1-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one (97 mg, 0.17 mmol) was treated with 90% TFA/water for 2 hours. Concentrate in vacuo and neutralized by passing through a column of MP-carbonate resin (2.0 g, 0.55 mmol/g eluting with MeOH/DCM/MeOH afforded 58 mg of (R)-3-(2-(((R)-1-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-(1-hydroxyethyl)oxazolidin-2-one as a waxy off-white foam. Separated the diastereomers via chiral SFC chromatography on an AD-H column (75 g/min, 120 bar, 21×250 mm) eluting 25% IPA/CO2 (v/v) to give (R)-3-(2-(((R)-1-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one and (R)-3-(2-(((S)-1-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one

Workup

  1. concentrationConcentrate in vacuo
  2. washeluting with MeOH/DCM/MeOH

Sources & evidence

ORD record
ord-666cc2b4005a4c97805c7e575f3a7959
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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