Tributylphosphine → Ethyl ({2-methyl-4-[(3-methyl-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}butyl)oxy]phenyl}oxy)acetate

HRID 1391763Notes

Reaction equation

HRID 1391763 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[N:7]=1)[OH:5].O[C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH3:37])[CH:25]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.P(CCCC)(CCCC)CCCC>C1COCC1>[CH3:37][C:26]1[CH:25]=[C:24]([O:5][CH:4]([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:14][CH:13]=3)[N:7]=2)[CH2:3][CH:2]([CH3:22])[CH3:1])[CH:36]=[CH:35][C:27]=1[O:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 21986458Ethyl (4-hydroxy-2-methylphenoxy)acetateHCID 586298133-Methyl-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}-1-butanol

Product 1

HCID 58629882Ethyl ({2-methyl-4-[(3-methyl-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}butyl)oxy]phenyl}oxy)acetateYield 47.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-methyl-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}-1-butanol (180 mg, 0.58 mmol) in dry THF (12 mL) under nitrogen was treated with ethyl (4-hydroxy-2-methylphenoxy)acetate (122 mg, 0.58 mmol) and cooled to 0° C. This was treated portion-wise with ADDP (0.3 g, 1.2 mmol), then drop-wise with nBu3P (0.29 mL, 1.2 mmol). The resulting pale yellow suspension allowed to warm to rt slowly over 16 hours. The solvent was removed under vacuum and the residue partitioned between EtOAc (60 mL) and water (60 mL) and the layers separated. The aqueous was re-extracted with EtOAc (60 mL) and the combined organic layer dried (Na2SO4) and reduced. Purification by SPE (silica, 10 g cartridge) eluting with cyclohexane:EtOAc (gradient 99:1 to 49:1) gave the title compound as a colourless oil (137 mg).

Workup

  1. temperatureto warm to rt slowly over 16 hours
  2. customThe solvent was removed under vacuum
  3. customthe residue partitioned between EtOAc (60 mL) and water (60 mL)
  4. customthe layers separated
  5. extractionThe aqueous was re-extracted with EtOAc (60 mL)
  6. dry with materialthe combined organic layer dried (Na2SO4)
  7. customPurification by SPE (silica, 10 g cartridge)
  8. washeluting with cyclohexane

Sources & evidence

ORD record
ord-d3c69a5198824365af9cff413cece0b9
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Reaction notes

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