Triphenylphosphine → 2-Hydroxy-4-(2-methoxy-4-vinylphenyl)-4-methyl-2-trifluoromethylvaleric acid methyl ester

HRID 1869387Notes

Reaction equation

HRID 1869387 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C:4]([OH:22])([C:18]([F:21])([F:20])[F:19])[CH2:5][C:6]([C:9]1[CH:14]=[CH:13][C:12](I)=[CH:11][C:10]=1[O:16][CH3:17])([CH3:8])[CH3:7].[CH2:24](C([Sn])=C(CCCC)CCCC)[CH2:25]CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:1][O:2][C:3](=[O:23])[C:4]([OH:22])([C:18]([F:21])([F:20])[F:19])[CH2:5][C:6]([C:9]1[CH:14]=[CH:13][C:12]([CH:24]=[CH2:25])=[CH:11][C:10]=1[O:16][CH3:17])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 179892492-Hydroxy-4-(4-iodo-2-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeric acid methyl esterHCID 53438229Tri(butyl)vinyltin

Product 1

HCID 179893052-Hydroxy-4-(2-methoxy-4-vinylphenyl)-4-methyl-2-trifluoromethylvaleric acid methyl esterYield 43.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1 g of 2-hydroxy-4-(4-iodo-2-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeric acid methyl ester, 860 mg of tributylvinyl tin, 103 mg of palladium-dibenzylidene acetone complex and 30 mg of triphenylphosphine in 17 ml of THF are refluxed under argon atmosphere for 57 hours. It is filtered through diatomaceous earth and completely concentrated by evaporation. After chromatography on silica gel (hexane/ethyl acetate 0->2%), 339 mg of 2-hydroxy-4-(2-methoxy-4-vinylphenyl)-4-methyl-2-trifluoromethylvaleric acid methyl ester is obtained. The latter is stirred with 56 mg of lithium aluminum hydride in 11 ml of diethyl ether at room temperature for 10 hours. It is added to saturated bicarbonate solution, filtered through diatomaceous earth and extracted with ethyl acetate. The organic phase is washed with bicarbonate solution and brine, dried (Na2SO4) and concentrated by evaporation. After chromatography on silica gel (hexane/ethyl acetate 0->10%), 148 mg of 2-hydroxy-4-(2-methoxy-4-vinylphenyl)-4-methyl-2-trifluoro-methylpentanol is obtained. The latter is hydrogenated in 4.3 ml of ethyl acetate with 14 mg of palladium on activated carbon under normal pressure with hydrogen. The batch is filtered through diatomaceous earth and completely concentrated by evaporation. 127 mg of 4-(4-ethyl-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentanol is obtained. The diol that is obtained is reacted with 0.29 ml of triethylamine and 280 mg of sulfur trioxide-pyridine complex in 1.3 ml of DMSO at room temperature in 10 hours of reaction time. It is added to saturated ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with water and brine, dried (Na2SO4) and concentrated by evaporation in a vacuum. After chromatography on silica gel (hexane/ethyl acetate 0->3%), 94 mg of the title compound is obtained as a colorless oil.

Workup

  1. filtrationIt is filtered through diatomaceous earth
  2. concentrationcompletely concentrated by evaporation

Sources & evidence

ORD record
ord-2914f742bb794c6bb0cf891b6832ec2f
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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