Diisopropylamine → 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-(5-phenylbenzoxazol-2-ylmethyl)pentan-2-ol

HRID 1070965Notes

Reaction equation

HRID 1070965 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][C:14]1[O:15][C:16]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][C:17]=2[N:18]=1.[F:29][C:30]([F:47])([F:46])[C:31](=[O:45])[CH2:32][C:33]([C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[O:43][CH3:44])([CH3:35])[CH3:34]>C1COCC1>[F:47][C:30]([F:29])([F:46])[C:31]([CH2:13][C:14]1[O:15][C:16]2[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:19][C:17]=2[N:18]=1)([OH:45])[CH2:32][C:33]([C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[O:43][CH3:44])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 112786Benzoxazole, 2-methyl-5-phenyl-HCID 100849201,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-oneHCID 178418339Butyllithium

Product 1

HCID 102389871,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-(5-phenylbenzoxazol-2-ylmethyl)pentan-2-olYield 76.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (0.246 mL, 1.6 M in hexanes) was added to a solution of diisopropyl amine (0.055 mL, 0.45 mmol) in anhydrous THF (5 mL) at 0° C. The reaction mixture was cooled to −78° C. and stirred for 15 minutes. 2-Methyl-5-phenyl benzoxazole (75 mg, 0.4 mmol) dissolved in anhydrous THF (2 mL) was added to this mixture dropwise. After the addition, the reaction mixture was stirred for 15 to 30 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (100 mg, 0.4 mmol) was added as a solution in anhydrous THF (2 mL) in one portion, the cold bath was removed and the reaction was stirred at room temperature for 12 hours. THF was evaporated under reduced pressure. Water (2 mL) was added to the residue and the mixture was extracted with three 5 mL portions of EtOAc. The extract was dried over magnesium sulfate. After evaporation, the residue was chromatographed on a silica gel column to provide 150 mg of the title compound as white crystals, m.p. 103° C.-104° C.

Workup

  1. additionwas added to this mixture dropwise
  2. additionAfter the addition
  3. stirringthe reaction mixture was stirred for 15 to 30 minutes
  4. customthe cold bath was removed
  5. stirringthe reaction was stirred at room temperature for 12 hours
  6. customTHF was evaporated under reduced pressure
  7. additionWater (2 mL) was added to the residue
  8. extractionthe mixture was extracted with three 5 mL portions of EtOAc
  9. dry with materialThe extract was dried over magnesium sulfate
  10. customAfter evaporation
  11. customthe residue was chromatographed on a silica gel column

Sources & evidence

ORD record
ord-b9ba1bc5a9584b30b49a218835996f88
Source dataset
uspto-grants-2005_06
Patent number
US06903215B2

Reaction notes

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