Sodium hydride → 5-{2-[2-Chloro-4-(pyrimidin-2-yloxy)-phenyl]-1-hydroxy-1-trifluoromethyl-propyl}-3-methyl-3H-benzooxazol-2-one

HRID 2096885Notes

Reaction equation

HRID 2096885 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:27])[C:10]([C:16]1[CH:17]=[CH:18][C:19]2[O:23][C:22](=[O:24])[N:21]([CH3:25])[C:20]=2[CH:26]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[H-].[Na+].Br[C:31]1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:31]2[N:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:27])[C:10]([C:16]1[CH:17]=[CH:18][C:19]2[O:23][C:22](=[O:24])[N:21]([CH3:25])[C:20]=2[CH:26]=1)([OH:15])[C:11]([F:12])([F:13])[F:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 783452-BromopyrimidineHCID 666969865-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one

Product 1

HCID 666970995-{2-[2-Chloro-4-(pyrimidin-2-yloxy)-phenyl]-1-hydroxy-1-trifluoromethyl-propyl}-3-methyl-3H-benzooxazol-2-oneYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one (100 mg, obtained in Example 172) was added to a suspension of NaH (60% in mineral oil, 20 mg) in DMF (4 mL). Stirring was continued for 30 minutes at r.t. The mixture was cooled to 0° C. and 2-bromopyrimidine (59 mg, [CAS Reg. No. 4595-60-2]) was added. Stirring was continued for 4 hours at r.t. The reaction mixture was poured into ice/water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a light yellow solid (35 mg, 30%). MS (m/e)=480.1 [M+H+].

Workup

  1. addition4595-60-2]) was added
  2. stirringStirring
  3. waitwas continued for 4 hours at r.t
  4. extractionextracted two times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-2190eb007faa4973b4e507c96b88a4d1
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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