Reaction #2371683

Reaction equation

water

2,5,6-trichloronicotinamide

tert-BuOK

2-(trifluoromethoxy)ethanol

→

5,6-dichloro-2-(2-(trifluoromethoxy)ethoxy)nicotinamide

Yield 8.0%

Solvents

EtOAc

DMF DME

Conditions

Workup

1. 1
   Otherthe organic layer was separated
2. 2
   Extractionthe aqueous phase was further extracted twice with EtOAc
3. 3
   Washthe combined organic layers were washed with brine twice
4. 4
   Dryingdried over Na2SO4
5. 5
   Concentrationconcentrated
6. 6
   Otherthe residue was purified by silica gel chromatography (Petroleum ether: EtOAc=1:0 to 5:1)

Procedure

To a mixture of compound 2-(trifluoromethoxy)ethanol (9.5 mmol) in DMF/DME (20/50 mL) was added 2,5,6-trichloronicotinamide (2.1 g, 9.5 mmol) and tert-BuOK (1.30 g, 11.4 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was poured into 100 mL of cold water, diluted with 100 mL of EtOAc, the organic layer was separated and the aqueous phase was further extracted twice with EtOAc, the combined organic layers were washed with brine twice, dried over Na2SO4 and concentrated, the residue was purified by silica gel chromatography (Petroleum ether: EtOAc=1:0 to 5:1) to give 5,6-dichloro-2-(2-(trifluoromethoxy)ethoxy)nicotinamide (0.24 g, 8%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 8.31 (s, 1H), 7.97 (s, 1H), 7.59 (s, 1H), 4.62 (t, 2H, J=4.0 Hz), 4.51 (t, 2H, J=4.0 Hz).

Source