tert-Butyl methyl ether → 4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfonyl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

HRID 531264Notes

Reaction equation

HRID 531264 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[S:30][C:29]([C:31]5[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=5[CH3:40])=[N:28][C:27]=4[C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:24][N:23]=[C:22](SC)[N:21]=3)[C@H:14]2[CH3:47])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[S:50]([O-:55])(O[O-])(=O)=[O:51].[K+].[K+].[CH3:58]OC(C)(C)C>CC#N.O>[F:49][C:2]([F:1])([F:48])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[S:30][C:29]([C:31]5[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=5[CH3:40])=[N:28][C:27]=4[C:41]([CH3:42])([CH3:43])[CH3:44])=[CH:24][N:23]=[C:22]([S:50]([CH3:58])(=[O:55])=[O:51])[N:21]=3)[C@H:14]2[CH3:47])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 10313463Potassium peroxymonosulphateHCID 900093044-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid2×

Product 1

HCID 900093774-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfonyl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid (INTERMEDIATE 51, 225 mg, 0.31 mmol) was dissolved in 10 mL CH3CN and 10 mL of water. Potassium peroxymonosulfate (5.1 g, 8.31 mmol) was added, and it was stirred at 60° C. for 2 hours. Then, it was worked up with water (100 mL) and t-butyl methyl ether (200 mL). The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated. The crude isolate was purified by silica gel chromatography, eluting with 60% ethyl acetate in hexanes to give the title compound as a slightly yellow solid (226 mg, 96% yield). LCMS (M+H)+: 757.1 1H NMR (DMSO, 500 MHz): δ 9.24 (s, 1H), 8.15 (s, 1H), 8.03 (s, 2H), 7.96 (s, 1H), 7.90 (s, 2H), 6.06 (m, 1H), 4.48 (m, 1H), 3.52 (s, 3H), 2.69 (s, 3H), 1.26 (s, 9H), 0.72 (d, J=6.0 Hz, 3H).

Workup

  1. dry with materialThe organic layer was dried over sodium sulfate
  2. filtrationfiltered
  3. concentrationthe filtrate concentrated
  4. customThe crude isolate
  5. customwas purified by silica gel chromatography
  6. washeluting with 60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-45a1a17bc67348689f0cb85ebb240dc1
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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