Water → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-(1-glycoloylpiperidin-4-yl)-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 2093221Notes

Reaction equation

HRID 2093221 reaction equation
C([O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[C:16]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][C:24]=3[CH2:33][N:34]3[C@@H:38]([CH3:39])[C@@H:37]([C:40]4[CH:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[C:42]([C:50]([F:53])([F:52])[F:51])[CH:41]=4)[O:36][C:35]3=[O:54])[C:17]([O:21][CH3:22])=[CH:18][C:19]=2[F:20])[CH2:10][CH2:9]1)=[O:7])(=O)C.C[O-].[Na+].O>CO>[F:53][C:50]([F:51])([F:52])[C:42]1[CH:41]=[C:40]([C@H:37]2[O:36][C:35](=[O:54])[N:34]([CH2:33][C:24]3[CH:25]=[C:26]([C:29]([F:31])([F:32])[F:30])[CH:27]=[CH:28][C:23]=3[C:16]3[CH:15]=[C:14]([CH:11]4[CH2:10][CH2:9][N:8]([C:6](=[O:7])[CH2:5][OH:4])[CH2:13][CH2:12]4)[C:19]([F:20])=[CH:18][C:17]=3[O:21][CH3:22])[C@H:38]2[CH3:39])[CH:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=1

Participants

5

Reactant 3

HCID 962WaterHCID 10942334Sodium MethoxideHCID 86630549HCID 86630549, compound

Product 1

HCID 25009326(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-(1-glycoloylpiperidin-4-yl)-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-{4-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-fluoro-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]piperidin-1 -yl}-2-oxoethyl acetate (24 mg, 0.031 mmol) in MeOH (1 mL) under N2 was added sodium methoxide (6.66 mg, 0.031 mmol) The resultant mixture was stirred at room temperature for 15 min. Water (10 mL) was added and the mixture was extracted with EtOAc (3×10 mL). The combined organic fractions were washed with brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-100% EtOAC/hexanes) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-5′-(1-glycoloylpiperidin-4-yl)-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one as a yellow gum. LCMS=737.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.87 (s, 1 H), 7.69 (s, 2 H), 7.68-7.60 (m, 2 H), 7.34-7.30 (m, 1 H), 6.96-6.91 (m, 1 H), 6.72 (d, J=11.9 Hz, 1 H), 5.44 (d, J=7.8 Hz, 1 H), 4.90 (d, J=15.8 Hz, 1 H), 4.78-4.70 (m, 1 H), 4.18-4.13 (m, 2 H), 3.78 (s, 3H), 3.62-3.54 (m, 1 H), 3.15-3.05 (m, 2 H), 2.82-2.73 (m, 1 H), 1.96-1.84 (m, 2 H), 1.70-1.52 (m, 4 H), 0.43-0.39 (m, 3 H).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×10 mL)
  2. washThe combined organic fractions were washed with brine (10 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash silica gel chromatography (0-100% EtOAC/hexanes)

Sources & evidence

ORD record
ord-a3bfb1919f2b4e5196c0ca63ed274c54
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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