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

HRID 1444430Notes

Reaction equation

HRID 1444430 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-eab38964b9954eaca853d325b8b14fe1
Source dataset
uspto-grants-2010_02
Patent number
US07662821B2

Reaction notes

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