2-(4-Fluorophenyl)acetic acid → 4-Fluorophenylacetyl chloride

HRID 1401354Notes

Reaction equation

HRID 1401354 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:15])=O>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([Cl:15])=[O:11])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 98372-(4-Fluorophenyl)acetic acidHCID 65578Oxalyl chloride

Product 1

HCID 37449884-Fluorophenylacetyl chlorideYield 104.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-fluorophenylacetic acid (1, scheme 1) (26.5 g, 172 mmol) in DCM (93 mL) was added oxalyl chloride (2 eq., 30.1 mL, 344 mmol) over 5 min and DMF (0.005 eq., 0.067 mL, 0.86 mmol) over 1 min. The reaction mixture was stirred at r.t for 2 h then concentrated. The residual DCM was removed as an azeotrope with toluene (2×20 mL) to afford intermediate 2-(4-fluorophenyl)acetyl chloride (1a) (30.85 g, 179 mmol, assumed quantitative yield) as yellow oil. Part of that material was used as is in the next step.

Workup

  1. concentrationthen concentrated
  2. customThe residual DCM was removed as an azeotrope with toluene (2×20 mL)

Sources & evidence

ORD record
ord-83f3b82250684d89acf12300e4e95546
Source dataset
uspto-grants-2014_12
Patent number
US08907091B2

Reaction notes

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