Trifluoroacetic acid → (R)-3-(2-(((S)-1-(1-(4-chloro-3-(trifluoromethoxy)phenyl)piperidin-4-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)-4-((S)-1-hydroxyethyl)oxazolidin-2-one

HRID 57486Notes

Reaction equation

HRID 57486 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[C:19]([F:20])=[CH:18][N:17]=[C:16]([NH:21][C@H:22]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([O:37][C:38]([F:41])([F:40])[F:39])[CH:31]=3)[CH2:26][CH2:25]2)[CH3:23])[N:15]=1)[CH3:7])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([N:27]2[CH2:28][CH2:29][CH:24]([C@@H:22]([NH:21][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])[C:19]([F:20])=[CH:18][N:17]=3)[CH3:23])[CH2:25][CH2:26]2)=[CH:31][C:32]=1[O:37][C:38]([F:39])([F:40])[F:41]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90415603(R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-(((S)-1-(1-(4-chloro-3-(trifluoromethoxy)phenyl)piperidin-4-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)oxazolidin-2-one

Product 1

HCID 90414342(R)-3-(2-(((S)-1-(1-(4-chloro-3-(trifluoromethoxy)phenyl)piperidin-4-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)-4-((S)-1-hydroxyethyl)oxazolidin-2-oneYield 88.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-(((S)-1-(1-(4-chloro-3-(trifluoromethoxy)phenyl)piperidin-4-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)oxazolidin-2-one (34 mg, 0.058 mmole) was dissolved in DCM (1 mL), TFA (1 mL) was added. The reaction solution was stirred for 2 hour at room temperature and was concentrated by rotary evaporation. The resulting residue was dissolved in DCM (2 mL) and water 2 mL) and the pH was adjusted to ˜9 with NH4OH. The DCM layer was separated and concentrated by rotary evaporation to afford 28 mg of the title product as a yellow oil (ratio of two peaks with same MS: 96/4% by LC-MS). (400 MHz, CD2Cl2) δ 8.22 (d, J=2.27 Hz, 1H), 7.31 (d, J=8.85 Hz, 1H), 6.88-6.79 (m, 2H), 5.12 (br s, 1H), 4.61-4.50 (m, 2H), 4.46-4.37 (m, 1H), 4.26-4.15 (m, 1H), 3.93 (br s, 1H), 3.77-3.68 (m, 2H), 3.20 (br s, 1H), 2.79-2.67 (m, 2H), 1.96-1.78 (m, 2H), 1.70-1.58 (m, 1H), 1.55-1.28 (m, 2H), 1.23 (d, J=6.63 Hz, 3H), 1.19 (d, J=7.19 Hz, 3H), HRMS(C) tR=4.47 min; MS m/z 548.1689 (M+H)+

Workup

  1. concentrationwas concentrated by rotary evaporation
  2. dissolutionThe resulting residue was dissolved in DCM (2 mL)
  3. customThe DCM layer was separated
  4. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-f93122fa3bb54268a2695d460cd9f3f9
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

Loading…