Sodium Carbonate → 4-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl ester

HRID 916030Notes

Reaction equation

HRID 916030 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]([OH:14])([C:10]([F:13])([F:12])[F:11])[CH2:6][C:7](Br)=[CH2:8])[CH3:2].[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[C:21](OC)[CH:22]=1.[C:28](=[O:31])([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.[Cl-].[NH4+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:15])[C:5]([OH:14])([C:10]([F:13])([F:12])[F:11])[CH2:6][C:7]([C:19]1[CH:18]=[C:17]([F:16])[CH:22]=[CH:21][C:20]=1[O:31][CH3:28])=[CH2:8])[CH3:2]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2763243(3-Fluoro-5-methoxyphenyl)boronic acidHCID 207961374-Bromo-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl ester

Product 1

HCID 207961364-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl esterYield 48%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A mixture of 500 mg (1.71 mmol) of 4-bromo-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl ester, 509 mg (3 mmol) of 3-fluoro-5-methoxyphenylboronic acid and 25 mg (0.022 mmol) of tetrakis(triphenylphosphine)palladium(0) in 4 mL of toluene, 2 mL of ethanol, and 1 mL of 2 M aqueous sodium carbonate was warmed at reflux. After 24 hours, the mixture was cooled and diluted with saturated aqueous ammonium chloride and extracted with three 10 mL portions of EtOAc. The combined organic layers were washed with three 5 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated. The crude solidified upon standing and was adsorbed onto silica gel and chromatographed on silica gel using EtOAc-hexanes (0:100, then 0.5:99.5, then 1:99, then 2:98) to afford partially purified product. Trituration with ether-hexane removed an insoluble by product. The filtrate was chromatographed on silica gel using dichloromethane-hexane (5:95, then 1:9, then 15:85, then 2:8, then 3:7, then 4:6) to afford 280 mg (48%) of 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl ester as an oil which solidified upon standing.

Workup

  1. temperaturewas warmed
  2. temperatureat reflux
  3. temperaturethe mixture was cooled
  4. extractionextracted with three 10 mL portions of EtOAc
  5. washThe combined organic layers were washed with three 5 mL portions of brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed on silica gel
  10. custom0.5:99.5, then 1:99, then 2:98) to afford partially purified product
  11. customTrituration with ether-hexane removed an insoluble by product
  12. customThe filtrate was chromatographed on silica gel

Sources & evidence

ORD record
ord-96261597910c443f83708dc5bbb177e0
Source dataset
uspto-grants-2007_09
Patent number
US07268152B2

Reaction notes

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