2-Methylbenzaldehyde → α,α-Difluoro-β-hydroxy-2-methylbenzenepropanoic acid

HRID 322990Notes

Reaction equation

HRID 322990 reaction equation
Br[C:2]([F:9])([F:8])[C:3]([O:5]CC)=[O:4].[CH3:10][C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[CH:13]=[O:14]>C1COCC1.C(OCC)(=O)C.[Zn]>[F:9][C:2]([F:8])([CH:13]([OH:14])[C:12]1[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=1[CH3:10])[C:3]([OH:5])=[O:4]

Participants

6

Reactant 2

HCID 107222-MethylbenzaldehydeHCID 69585Ethyl bromodifluoroacetate

Product 1

HCID 22010354α,α-Difluoro-β-hydroxy-2-methylbenzenepropanoic acidYield 44.5%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl bromodifluoroacetate (5.6 g) and 2-methylbenzaldehyde (3 g) in THF (25 mL) is added dropwise to a refluxing suspension of activated zinc dust (2.1 g) in THF (25 mL) and refluxing continued for a further 4 hours. The reaction is allowed to cool to ambient temperature, filtered through hyflo and concentrated in vacuo to give a yellow solid. The solid is taken up in ethyl acetate (50 mL) and washed with brine which leads to the formation of a white precipitate which is filtered off then partitioned between ethyl acetate (50 mL) and 1 N HCl (50 mL). The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated in vacuo to give (RS)-2,2-difluoro-3-hydroxy-3-(2-methylphenyl)propanoic acid as a yellow solid (2.4 g)

Workup

  1. temperaturerefluxing
  2. filtrationfiltered through hyflo
  3. concentrationconcentrated in vacuo
  4. customto give a yellow solid
  5. washwashed with brine which
  6. filtrationis filtered off
  7. customthen partitioned between ethyl acetate (50 mL) and 1 N HCl (50 mL)
  8. washThe organic phase is washed with water
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-13feaa4164084c12872d0c3025d1e6f3
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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