Water → 1,1,1,3,3,3-hexafluoro-2-[4-(methoxymethoxy)-3-propyl-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]phenyl]propan-2-ol

HRID 552448Notes

Reaction equation

HRID 552448 reaction equation
C([Li])CCC.Br[C:7]1[C:12]([CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[C:11]([CH2:21][CH2:22][CH3:23])[C:10]([O:24][CH2:25][O:26][CH3:27])=[CH:9][CH:8]=1.[F:28][C:29]([F:37])([F:36])[C:30]([C:32]([F:35])([F:34])[F:33])=[O:31].O>O1CCCC1>[F:28][C:29]([F:37])([F:36])[C:30]([C:7]1[CH:8]=[CH:9][C:10]([O:24][CH2:25][O:26][CH3:27])=[C:11]([CH2:21][CH2:22][CH3:23])[C:12]=1[CH2:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1)([OH:31])[C:32]([F:35])([F:34])[F:33]

Participants

6

Reactant 4

HCID 962WaterHCID 12695HexafluoroacetoneHCID 579008212-(6-bromo-3-(methoxymethoxy)-2-propylbenzyloxy)tetrahydro-2H-pyraneHCID 178418339Butyllithium

Product 1

HCID 579008411,1,1,3,3,3-hexafluoro-2-[4-(methoxymethoxy)-3-propyl-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]phenyl]propan-2-olYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere, n-butyl lithium (1.58 mol/L hexane solution 1.55 mL, 2.45 mmol) was dropped at −78° C. into a solution of 2-(6-bromo-3-(methoxymethoxy)-2-propylbenzyloxy)tetrahydro-2H-pyrane (725 mg, 1.75 mmol) in tetrahydrofuran (8 mL). The mixture was stirred at the same temperature for 15 minutes and then stirred at the elevated temperature of −45° C. for 1.5 hours. A tetrahydrofuran (4 mL) solution of hexafluoroacetone was dropped at −78° C., and the mixture was stirred at 0° C. for 5 hours and then stirred at room temperature for 12 hours. The reaction solution was added with water and extracted with ethyl acetate. Subsequently, the organic layer was washed with saturated saline, dried using anhydrous sodium sulfate, and concentrated in vacuum. The residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (728 mg, 90%) was obtained as colorless oil.

Workup

  1. stirringstirred at the elevated temperature of −45° C. for 1.5 hours
  2. stirringthe mixture was stirred at 0° C. for 5 hours
  3. stirringstirred at room temperature for 12 hours
  4. extractionextracted with ethyl acetate
  5. washSubsequently, the organic layer was washed with saturated saline
  6. customdried
  7. concentrationconcentrated in vacuum
  8. customThe residue was purified by silica-gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-90ccc6d0fcfa4c278a17aa044b4bca8f
Source dataset
uspto-grants-2011_05
Patent number
US07951822B2

Reaction notes

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