Hydrochloric Acid → 4,4-difluoro-1-(3-fluoro-4-methoxyphenyl)butane-1,3-dione

HRID 1941689Notes

Reaction equation

HRID 1941689 reaction equation
[F:1][CH:2]([F:8])[C:3](OCC)=[O:4].C[O-].[Na+].[F:12][C:13]1[CH:14]=[C:15]([C:21](=[O:23])[CH3:22])[CH:16]=[CH:17][C:18]=1[O:19][CH3:20].Cl>C(OC)(C)(C)C>[F:1][CH:2]([F:8])[C:3](=[O:4])[CH2:22][C:21]([C:15]1[CH:16]=[CH:17][C:18]([O:19][CH3:20])=[C:13]([F:12])[CH:14]=1)=[O:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9961Ethyl difluoroacetateHCID 968281-(3-Fluoro-4-methoxyphenyl)ethan-1-oneHCID 10942334Sodium Methoxide

Product 1

HCID 154849694,4-difluoro-1-(3-fluoro-4-methoxyphenyl)butane-1,3-dione

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

Ethyl difluoroacetate (4.06 g, 32.7 mmol) was placed in a 250 mL Erlenmeyer flask, and dissolved in methyl tert-butyl ether (50 mL). To the stirred solution was added 25% sodium methoxide (7.07 g, 32.7 mmol) followed by 3′-fluoro-4′-methoxyacetophenone from Step 1 (5.0 g, 29.7 mmol). After stirring for 16 hours, 1N HCl (50 mL) was added. The organic layer was collected, washed with water (2×50 mL), dried over anhydrous MgSO4, filtered, and added to hexanes to precipitate a tan solid (7.0 g, 96%): mp 70°-72° C.; 1H NMR (DMSO-d6) 8.0 (m, 3H), 7.3 (t, 1H), 6.9 (s, 1H), 6.5 (t, 1H), 3.9 (s, 3H).

Workup

  1. customThe organic layer was collected
  2. washwashed with water (2×50 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. additionadded to hexanes
  6. customto precipitate a tan solid (7.0 g, 96%)

Sources & evidence

ORD record
ord-0df9e8146a794d75a866aff5de6bb086
Source dataset
uspto-grants-2013_03
Patent number
USRE044048E1

Reaction notes

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