Hydrochloric Acid → 4-(5-Bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid ethyl ester

HRID 1869345Notes

Reaction equation

HRID 1869345 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[Br:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1.[CH2:14]([O:16][C:17](=[O:28])[C:18]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH2:19][C:20](=[CH2:22])[CH3:21])[CH3:15].Cl>>[CH2:14]([O:16][C:17](=[O:28])[C:18]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH2:19][C:20]([C:10]1[CH:11]=[C:6]([Br:5])[CH:7]=[CH:8][C:9]=1[O:12][CH3:13])([CH3:22])[CH3:21])[CH3:15]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 77304-BromoanisoleHCID 6451240Aluminum(III) ChlorideHCID 17935595Ethyl 2-hydroxy-4-methyl-2-(trifluoromethyl)pent-4-enoate

Product 1

HCID 179892594-(5-Bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid ethyl esterYield 51.8%

Procedure

34.45 g (258.91 mmol) of aluminum trichloride is introduced into 354.35 g (237.02 mmol) of 4-bromoanisole. 38.95 g (172.19 mmol) of 2-hydroxy-4-methylene-2-(trifluoromethyl)pentanoic acid ethyl ester is added in drops to this mixture within one hour. After stirring overnight at room temperature, the batch is added to ice water and made acidic with 10% hydrochloric acid. After 3× extraction with ethyl acetate, the combined organic extracts are washed with 1N hydrochloric acid and brine. After drying on magnesium sulfate, the solvent is spun off. Most of the excess 4-bromoanisole is distilled off (10 mbar; bath temperature 110° C.). After chromatography on silica gel (mobile solvent ethyl acetate/hexane), 36.87 g (51.8%) of the desired compound is obtained.

Workup

  1. extractionAfter 3× extraction with ethyl acetate
  2. washthe combined organic extracts are washed with 1N hydrochloric acid and brine
  3. customAfter drying on magnesium sulfate
  4. distillationMost of the excess 4-bromoanisole is distilled off (10 mbar; bath temperature 110° C.)

Sources & evidence

ORD record
ord-2ca242676fa54ef284e22b0b0f5da098
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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