Water → 4-Fluorophenylacetyl chloride

HRID 2055884Notes

Reaction equation

HRID 2055884 reaction equation
O.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.CN(C)C=O.C(Cl)(=O)C([Cl:21])=O>C1(C)C=CC=CC=1>[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([Cl:21])=[O:12])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 98372-(4-Fluorophenyl)acetic acidHCID 65578Oxalyl chloride

Product 1

HCID 37449884-Fluorophenylacetyl chlorideYield 90%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Into a 1-L three-neck flask equipped with a mechanical stirrer, an addition funnel, and a nitrogen bubbler vented to a water scrubber was placed 60.0 g (0.389 mol) of 4-fluorophenylacetic acid, 0.18 g, 0.002 mol) of N,N-dimethylformamide and 250 g of toluene. The addition funnel was charged with 50.4 g (0.397 mol) of oxalyl chloride and added to the reaction mixture over a 10 minute period resulting in gas evolution (4.7° C. exotherm was observed). The reaction mixture was stirred at ambient temperature for 2.5 hours (gas evolution complete) and the head space of the reaction flask was sparged with nitrogen for 10 minutes before storing the material. HPLC assay of the solution indicated that 19.1 wt % of the solution was 4-fluoroacetyl chloride, thus affording a 99% yield. Purification of crude 4-fluorophenylacetyl chloride by vacuum distillation (57-58° C., 0.15 mm Hg) affords 4-fluorophenylacetyl chloride as a clear liquid in 90% yield.

Workup

  1. customInto a 1-L three-neck flask equipped with a mechanical stirrer, an addition funnel
  2. additionadded to the reaction mixture over a 10 minute period
  3. customresulting in gas evolution (4.7° C. exotherm was observed)
  4. customthe head space of the reaction flask was sparged with nitrogen for 10 minutes
  5. customthus affording a 99% yield
  6. customPurification of crude 4-fluorophenylacetyl chloride
  7. distillationby vacuum distillation (57-58° C., 0.15 mm Hg)

Sources & evidence

ORD record
ord-257a8388f5374f40a0895ff246cc4387
Source dataset
uspto-grants-2008_02
Patent number
US07332607B2

Reaction notes

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