Methanol → alpha-Acetyl-2-bromo-4-fluorobenzeneacetonitrile

HRID 514239Notes

Reaction equation

C[O-:2].[Na+].CO.[C:6]1([CH3:12])C=CC=CC=1.[Br:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[CH2:21][C:22]#[N:23]>C(OCC)(=O)C.O>[C:6]([CH:21]([C:15]1[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=1[Br:13])[C:22]#[N:23])(=[O:2])[CH3:12]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of sodium methoxide in methanol (25%, 34 mL, 157 mmol) was combined with toluene (200 mL). The methanol was then distilled off at 90° C. using a Dean-Stark trap. After the solution was cooled to 70° C., 2-bromo-4-fluorobenzeneacetonitrile (21.4 g, 100 mmol) dissolved in ethyl acetate (40 mL) was added from a dropping funnel over 20 min with mechanical stirring. At this point additional toluene (150 mL) was added to facilitate stirring of a voluminous light pink precipitate. The reaction mixture was poured into water, and the organic phase was separated. The aqueous phase was acidified and extracted with ethyl acetate. The ethyl acetate phase was dried and concentrated under reduced pressure to provide the intermediate compound α-acetyl-2-bromo-4-fluorobenzeneacetonitrile as a crude oil.

Workup

distillationThe methanol was then distilled off at 90° C.
additionwas added from a dropping funnel over 20 min with mechanical stirring
customthe organic phase was separated
extractionextracted with ethyl acetate
dry with materialThe ethyl acetate phase was dried
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-0a04fffe5e1449f6864c7bacc3a19a61
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09107412B2

Reaction notes

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