Acetyl chloride → 5-Acetyl-2-[2-chloro-5-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbonitrile

HRID 924686Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[NH:13][CH:14]=[CH:15][C:16]=1[C:17]#[N:18].[C:19](Cl)(=[O:21])[CH3:20]>C1(C)C=CC=CC=1.CCOC(C)=O.[Zn]>[C:19]([C:14]1[NH:13][C:12]([C:3]2[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=2[Cl:1])=[C:16]([C:17]#[N:18])[CH:15]=1)(=[O:21])[CH3:20]

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 2-[2-chloro-5-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbonitrile (450 mg, 1.66 mmol) in toluene (3 mL) was added acetyl chloride (0.176 mL, 2.49 mmol) at room temperature, under nitrogen, and zinc (217 mg, 3.32 mmol). The mixture was allowed to stir for 3 h at 80° C. The mixture was cooled to room temperature, diluted with EtOAc and washed with water. The aqueous layer was separated and extracted twice with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude material was chromatographed on silica gel (0 to 10% EtOAc/hexane) to afford the title compound (386 mg, 74%).

Workup

temperatureThe mixture was cooled to room temperature
washwashed with water
customThe aqueous layer was separated
extractionextracted twice with EtOAc
washThe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe crude material was chromatographed on silica gel (0 to 10% EtOAc/hexane)

Sources & evidence

ORD record: ord-2f882c2e8455480482049b8b28ab575a
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09283224B2

Reaction notes

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