4-Chlorobutyryl chloride → 1-(6-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-yl)pyrrolidin-2-one

To a mixture of 1-(6-amino-4-chloro-3′-fluoro-5-methylbiphenyl-2-yl)ethanone (100 mg, 0.4 mmol) and 4-dimethylaminopyridine (52.8 mg, 0.432 mmol) in tetrahydrofuran (1 mL) was added 4-chlorobutanoyl chloride (0.044 mL, 0.40 mmol). The reaction was stirred at room temperature for 1 hour. Potassium tert-butoxide (1.0 M) in tetrahydrofuran (0.79 mL, 0.79 mmol) was added and the resulting mixture was stirred at room temperature for 2 hours, then quenched with aq. ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried and evaporated. The resulting residue was purified on silica gel, eluting with 0 to 50% ethyl acetate in hexane, to give the product (40 mg, 30%). LCMS calculated for C19H18ClFNO2 (M+H)+: m/z=346.1. found: 346.1.

1. stirringthe resulting mixture was stirred at room temperature for 2 hours
2. customquenched with aq. ammonium chloride
3. extractionextracted with ethyl acetate
4. washThe combined organic layers were washed with water, brine
5. customdried
6. customevaporated
7. customThe resulting residue was purified on silica gel
8. washeluting with 0 to 50% ethyl acetate in hexane

ORD record

ord-e8fdab7e8e4d4477ab95268edd4ecead

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096600B2