Sodium hydride → HCID 86698169, compound

HRID 623881Notes

Reaction equation

HRID 623881 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[N:4]=[C:5]([C:16]2[CH:17]=[CH:18][C:19]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)=[N:20][CH:21]=2)[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1.[H-].[Na+].[CH2:33]([C:35]([CH2:42]OS(C1C=CC(C)=CC=1)(=O)=O)([CH2:40][CH3:41])[C:36]([O:38][CH3:39])=[O:37])[CH3:34].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH2:33]([C:35]([CH2:42][O:28][C:25]1[CH:24]=[CH:23][C:22]([C:19]2[CH:18]=[CH:17][C:16]([C:5]3[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:13])[CH3:14])[CH:7]=[C:3]([C:2]([F:1])([F:29])[F:30])[N:4]=3)=[CH:21][N:20]=2)=[CH:27][CH:26]=1)([CH2:40][CH3:41])[C:36]([O:38][CH3:39])=[O:37])[CH3:34]

Participants

7

Reactant 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 86698170HCID 86698170, compoundHCID 136378634HCID 136378634, compound

Product 1

HCID 86698169HCID 86698169, compoundYield 61.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

In N,N-dimethylformamide (1.4 mL) was dissolved 4-{5-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridin-2-yl}phenol (305 mg), 60% sodium hydride (34 mg) was added to the solution at room temperature and the mixture was stirred for one hour. To the reaction mixture was added an N,N-dimethylformamide (1 mL) solution containing methyl 2-ethyl-2-(p-tolylsulfonyloxymethyl)-butanoate (264 mg) under ice-cooling. The reaction mixture was stirred at 100° C. overnight. To the reaction mixture was added 60% sodium hydride (9 mg) under ice-cooling, and the mixture was stirred at 100° C. overnight. To the reaction mixture were added a saturated aqueous ammonium chloride solution and ethyl acetate, and the liquids were separated. The aqueous layer was separated, and extracted with ethyl acetate. The organic layers were combined, washed with water and saturated brine in this order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=95:5 to 50:50) to obtain methyl 2-ethyl-2-[[4-[5-[4-(trifluoromethyl)-1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]-2-pyridyl]phenoxy]methyl]-butanoate (248 mg).

Workup

  1. additionwas added to the solution at room temperature
  2. temperaturecooling
  3. stirringThe reaction mixture was stirred at 100° C. overnight
  4. temperaturecooling
  5. stirringthe mixture was stirred at 100° C. overnight
  6. customthe liquids were separated
  7. customThe aqueous layer was separated
  8. extractionextracted with ethyl acetate
  9. washwashed with water and saturated brine in this order
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=95:5 to 50:50)

Sources & evidence

ORD record
ord-a44c7c6a6a82411bb5a7d2dc411ed12e
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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