Ammonium Chloride → Methyl 3-(3,5-difluoropyridin-2-yl)-2-(2-fluorophenyl)-3-oxopropanoate

Temperature

-78 °C

21.4 ml (21.4 mmol) of lithium hexamethyldisilazide (1.0 M in THF) were initially charged in THF (30 ml) under argon and a solution of 3.00 g (17.8 mmol) of methyl 2-fluorophenylacetate in THF (15 ml) was added dropwise at −78° C. The reaction mixture was stirred at −78° C. for 1 h, and then a solution of 3.80 g (21.4 mmol) of the compound from example 3A in THF (15 ml) was added dropwise. The solution was stirred at −78° C. for 1 h, then brought to RT, and saturated aqueous ammonium chloride solution was added in portions. The mixture was diluted with water and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was stirred with MTBE, the solid was filtered off and the filtrate was concentrated. Silica gel chromatography (mobile phase:cyclohexane-ethyl acetate: 30:1, 20:1) of the residue gave 3.66 g (87% pure, 57% of theory) of the title compound. The crude product was reacted without further purification.

1. stirringThe solution was stirred at −78° C. for 1 h
2. custombrought to RT
3. extractionextracted twice with ethyl acetate
4. dry with materialThe combined organic phases were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. stirringThe residue was stirred with MTBE
8. filtrationthe solid was filtered off
9. concentrationthe filtrate was concentrated

ORD record

ord-a74c388e715147ac95a05f40df668cbc

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090609B2