Tributylphosphine → Ethyl 3-[2-methyl-4-({[4'-(trifluoromethyl)-3-biphenylyl]methyl}oxy)phenyl]propanoate

HRID 1391733Notes

Reaction equation

HRID 1391733 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][OH:16])[CH:10]=2)=[CH:5][CH:4]=1.P(CCCC)(CCCC)CCCC.O[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])=[C:35]([CH3:46])[CH:34]=1>C1COCC1>[CH3:46][C:35]1[CH:34]=[C:33]([O:16][CH2:15][C:11]2[CH:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:17])([F:18])[F:1])=[CH:8][CH:7]=3)[CH:14]=[CH:13][CH:12]=2)[CH:38]=[CH:37][C:36]=1[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 144680034'-(Trifluoromethyl)[1,1'-biphenyl]-3-methanolHCID 21986481Ethyl 3-(4-hydroxy-2-methylphenyl)propanoate

Product 1

HCID 69212754Ethyl 3-[2-methyl-4-({[4'-(trifluoromethyl)-3-biphenylyl]methyl}oxy)phenyl]propanoateYield 66.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of [4′-(trifluoromethyl)-3-biphenylyl]methanol (121 mg, 0.48 mmol) in dry THF (5 mL) under nitrogen at 0° C. (ice/water bath) was added nBu3P (240 μL, 0.96 mmol) followed by ethyl 3-(4-hydroxy-2-methylphenyl)propanoate (100 mg, 0.48 mmol) and then ADDM (246 mg, 0.96 mmol) portion-wise. The mixture was stirred at 0° C. for 1 hour, allowed to warm to rt over 21 hours and then partitioned between water and EtOAc, and the layers separated. The aqueous layer was then extracted with EtOAc and the combined organic extract washed with water and then brine, dried (Na2SO4) and the solvent removed under vacuum. Purification by flash chromatography (silica) eluting with cyclohexane:EtOAc (15:1) afforded the title compound as a clear oil (141 mg).

Workup

  1. temperatureto warm to rt over 21 hours
  2. custompartitioned between water and EtOAc
  3. customthe layers separated
  4. extractionThe aqueous layer was then extracted with EtOAc
  5. extractionthe combined organic extract
  6. washwashed with water
  7. dry with materialbrine, dried (Na2SO4)
  8. customthe solvent removed under vacuum
  9. customPurification by flash chromatography (silica)
  10. washeluting with cyclohexane:EtOAc (15:1)

Sources & evidence

ORD record
ord-02fba1fd6e1a4ad79cea87c165b9f885
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Reaction notes

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