Sodium hydride → HCID 86704651, compound

HRID 1508604Notes

Reaction equation

HRID 1508604 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[NH:14][C@H:13]2[CH3:18])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[H-].[Na+].CS(O[CH2:26][C:27]1[C:32]([C:33]2[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[C:36]([F:42])=[CH:35][C:34]=2[O:43][CH3:44])=[CH:31][N:30]=[C:29]([S:45][CH3:46])[N:28]=1)(=O)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[N:14]([CH2:26][C:27]3[C:32]([C:33]4[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[C:36]([F:42])=[CH:35][C:34]=4[O:43][CH3:44])=[CH:31][N:30]=[C:29]([S:45][CH3:46])[N:28]=3)[C@H:13]2[CH3:18])[CH:5]=[C:6]([C:8]([F:9])([F:11])[F:10])[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68080210HCID 68080210, compoundHCID 86704652HCID 86704652, compound

Product 1

HCID 86704651HCID 86704651, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 67(c)—(Table 8), 145 mg, 0.447 mmol) in THF (4 mL) at 0° C. was added sodium hydride (60 wt %, 23.3 mg, 0.582 mmol). The reaction was stirred at 0° C. for 1 hour and a solution of {5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-2-(methylsulfanyl)pyrimidin-4-yl}methyl methanesulfonate (188 mg, 0.470 mmol) in THF (500 μL) was added. The reaction was allowed to warm to room temperature and was stirred at room temperature for 6 hours. The reaction was quenched with HCl (1 N) and the reaction was poured into saturated aqueous NaHCO3 and ethyl acetate. The organic was washed with brine, was dried (Na2SO4), filtered, and concentrated. The resultant residue was purified by column chromatography to yield (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-3-({5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-2-(methylsulfanyl)pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (190 mg, 0.302 mmol). LCMS calc.=628.1/630.1. found=628.2/630.2

Workup

  1. temperatureto warm to room temperature
  2. stirringwas stirred at room temperature for 6 hours
  3. customThe reaction was quenched with HCl (1 N)
  4. additionthe reaction was poured into saturated aqueous NaHCO3 and ethyl acetate
  5. washThe organic was washed with brine
  6. dry with materialwas dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resultant residue was purified by column chromatography

Sources & evidence

ORD record
ord-3c358b4aef7f460895f2a123a87ef522
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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