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

Temperatur

-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 12A 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 sulphate, filtered and concentrated. The residue was stirred with MTBE, the solids were filtered off and the filtrate was concentrated. Silica gel chromatography (eluent: 30:1, 20:1 cyclohexane-ethyl acetate) of the residue gave 3.66 g (87% purity, 57% of theory) of the title compound. The crude product was converted 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 sulphate
5. filtrationfiltered
6. concentrationconcentrated
7. stirringThe residue was stirred with MTBE
8. filtrationthe solids were filtered off
9. concentrationthe filtrate was concentrated

ORD-Eintrag

ord-2ee125d9ad75483a9f02c7ce0fb02956

Quelldatensatz

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09023849B2