Trifluoroacetic acid water → (R)-3-(2-(((R)-1-(3-(4-chlorophenyl)isoxazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one

HRID 57491Notes

Reaction equation

HRID 57491 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]([Cl:34])=[CH:30][CH:29]=3)[CH:24]=2)[CH3:22])[N:15]=1)[CH3:7])(C)(C)C.C(O)(C(F)(F)F)=O.O>>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([C:25]2[CH:24]=[C:23]([C@@H:21]([NH:20][C:16]3[N:15]=[C:14]([N:9]4[C@@H:8]([C@H: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:29][CH:30]=1.[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([C:25]2[CH:24]=[C:23]([C@H:21]([NH:20][C:16]3[N:15]=[C:14]([N:9]4[C@@H:8]([C@H: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:29][CH:30]=1

Participants

4

Reactant 2

HCID 22392675Trifluoroacetic acid waterHCID 90415932(4R)-3-[2-[[1-[3-(4-Chlorophenyl)-5-isoxazolyl]ethyl]amino]-4-pyrimidinyl]-4-[(1R)-1-(1,1-dimethylethoxy)ethyl]-2-oxazolidinone

Product 2

HCID 90414298(R)-3-(2-(((R)-1-(3-(4-chlorophenyl)isoxazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-oneHCID 90414332(R)-3-(2-(((S)-1-(3-(4-chlorophenyl)isoxazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one

Procedure

(4R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-((1-(3-(4-chlorophenyl)isoxazol-5-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one (3.50 g, 2.88 mmol) was treated with 90% TFA/water for 2 hours. Concentrated in vacuo and neutralized by passing through a column of MP-carbonate resin (6.0 g, 0.55 mmol/g eluting with MeOH/DCM/MeOH afforded the diastereomeric mixture. Chiral SFC chromatography on an OJ-H column (75 g/min, 120 bar, 21×250 mm) eluting 30% IPA+10 mM NH4OH/CO2 (v/v) to give (R)-3-(2-(((S)-1-(3-(4-chlorophenyl)isoxazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one and (R)-3-(2-(((R)-1-(3-(4-chlorophenyl)isoxazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one.

Workup

  1. concentrationConcentrated in vacuo
  2. washeluting with MeOH/DCM/MeOH
  3. customafforded the diastereomeric mixture
  4. washChiral SFC chromatography on an OJ-H column (75 g/min, 120 bar, 21×250 mm) eluting 30% IPA+10 mM NH4OH/CO2 (v/v)

Sources & evidence

ORD record
ord-9f3b855d85b94319b687da9d8dfb12ed
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

Loading…