1,1'-Carbonyldiimidazole → Methyl 3-oxo-4-(2,4,5-trifluorophenyl)butanoate

To a solution of 2,4,5-trifluorophenyl acetic acid (42.2 g, 222 mmol) in THF (400 mL) was added 1,1′-carbonyldiimidazole (39.5 g, 244 mmol) in portions at 0° C. The mixture was warmed to room temperature for 1 h, stirred at room temperature for another 1 h, and transferred to another flask containing 1.1 equivalent of methyl malonic acid magnesium salt. The stirring was continued for 24 h and quenched with 1N HCl. The mixture was extracted with dichloromethane and the organic phase was washed with saturated sodium bicarbonate, then brine, then dried over sodium sulfate, filtered and evaporated. The residue was crystallized from isopropanol/water to give 42.2 g (77.3%) of off-white solid. 1H NMR (300 MHz, CDCl3) 7.10-6.90 (m, 2H), 3.85 (s, 2H), 3.78 (s, 3H), 3.55 (s, 2H)

1. customtransferred to another flask
2. waitThe stirring was continued for 24 h
3. customquenched with 1N HCl
4. extractionThe mixture was extracted with dichloromethane
5. washthe organic phase was washed with saturated sodium bicarbonate
6. dry with materialbrine, then dried over sodium sulfate
7. filtrationfiltered
8. customevaporated
9. customThe residue was crystallized from isopropanol/water

ORD record

ord-d96ffd2ecc214b56b29287cc33abc4ee

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278486B2