Ethyl Acetate → N-(4-cyano-2-fluoro-5-(trifluoromethyl)phenyl)acetamide

HRID 1504944Notes

Reaction equation

Br[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([NH:12][C:13](=[O:15])[CH3:14])=[C:4]([F:16])[CH:3]=1.[C:17]([Cu])#[N:18].CCOC(C)=O>CN(C=O)C>[C:17]([C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([NH:12][C:13](=[O:15])[CH3:14])=[C:4]([F:16])[CH:3]=1)#[N:18]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of compound 23 (300 mg, 1 mmol), CuCN (355 mg, 4 mmol) in DMF (6 mL) was heated at 150° C. under N2 overnight. The reaction mixture was cooled to room temperature and then poured into ice water. EtOAc was added and the insoluble solid was filtered off (rinsed with EtOAc). The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with aq.NaHCO3 and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified with silica gel chromatography (PE:EtOAc=4:1) to afford the title compound 24 (140 mg, 28%) as a white solid. 1H NMR (400 MHz, CDCl3) δ8.99 (d, 1H, J=7.2 Hz), 7.55 (d, 1H, J=10.0 Hz), 2.92 (s, 3H).

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationthe insoluble solid was filtered off
wash(rinsed with EtOAc)
customThe organic layer was separated
extractionthe aqueous layer was extracted with EtOAc
washThe combined organic layers were washed with aq
dry with materialNaHCO3 and brine, dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified with silica gel chromatography (PE:EtOAc=4:1)

Sources & evidence

ORD record: ord-fde8eaaa87d243409581d7a5eada02e4
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216957B2

Reaction notes

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