4-(5-Chloro-2-fluorobenzoyl)nicotinic acid → 4-(5-Chloro-2-fluorobenzyl)nicotinic acid

Temperatur

80 °C

Zinc-copper couple (0.75 g) is added to a stirred mixture of 4-(5-chloro-2-fluorobenzoyl)nicotinic acid and 3-(5-chloro-2-fluorobenzoyl)isonicotinic acid of Preparative Example 11 (94/6 on a molar base; 0.60 g) in 75% formic acid. The exothermic and effervescent reaction mixture is stirred for 15 min before heating to 80° C. for 2 hours. After cooling to 40° C., the mixture is filtered through a sintered glass funnel. The solid is washed with 75% formic acid (1×5 mL) and ethyl acetate (2×5 mL). The mixture is concentrated by roto-evaporation to about 2 mL. The orange oil obtained is dissolved in 0.5N HCl (3 mL) and extracted with ethyl acetate (3×10 mL), then saturated with NaCl and extracted with ethyl acetate/1,2-dimethoxyethane (2×5 mL). The combined extracts are dried with Na2SO4 and the solvents removed by roto-evaporation to yield a yellow foam. The foam (0.541 g) is recrystallized in hot acetonitrile (1 mL) to yield 4-(5-chloro-2-fluorobenzyl)nicotinic acid (0.142 g).

1. temperatureAfter cooling to 40° C.
2. filtrationthe mixture is filtered through a sintered glass funnel
3. washThe solid is washed with 75% formic acid (1×5 mL) and ethyl acetate (2×5 mL)
4. concentrationThe mixture is concentrated by roto-evaporation to about 2 mL
5. customThe orange oil obtained
6. extractionextracted with ethyl acetate (3×10 mL)
7. extractionsaturated with NaCl and extracted with ethyl acetate/1,2-dimethoxyethane (2×5 mL)
8. dry with materialThe combined extracts are dried with Na2SO4
9. customthe solvents removed by roto-evaporation
10. customto yield a yellow foam
11. customThe foam (0.541 g) is recrystallized in hot acetonitrile (1 mL)

ORD-Eintrag

ord-41c91eeb30c04feebbae45fa337974c0

Quelldatensatz

uspto-grants-1997_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05604246