2,2,2-Trifluoroethanol → Ethyl 5-chloro-6-(2,2,2-trifluoroethoxy)nicotinate

Temperature

-73 °C

To a solution of ethyl 5,6-dichloronicotinate (6.28 g, 28.5 mmol) and 2,2,2-trifluoroethanol (2.71 ml, 37.1 mmol) in THF (90 ml) at −73° C. was added NaHMDS (37.1 ml, 37.1 mmol). The reaction was stirred at −73° C. for 30 minutes, then at 0° C. for 5 hours. The reaction was quenched with 30 mL saturated NH4Cl solution. The reaction mixture was then poured into 50 mL brine and phases were separated. The aqueous layer was extracted with DCM (2×100 mL). The combined organics were dried (Na2SO4) and concentrated. Silica gel chromatography with 100% heptane to 30% EtOAc in heptane provided final product (7.51 g). LCMS m/z 284.1 (M+H)+, Rt 1.07 min.

1. waitat 0° C. for 5 hours
2. customThe reaction was quenched with 30 mL saturated NH4Cl solution
3. additionThe reaction mixture was then poured into 50 mL brine and phases
4. customwere separated
5. extractionThe aqueous layer was extracted with DCM (2×100 mL)
6. dry with materialThe combined organics were dried (Na2SO4)
7. concentrationconcentrated

ORD record

ord-59bd001e9ff646b98d34070e321f5f38

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957068B2