Reacción #85718

Ecuación de reacción

2,2,2-trifluoroethanol

ethyl 2-oxocyclohexanecarboxylate

(R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

Cs2CO3

→

(R)—N—((S)-1-(2,5-difluoro-4-(2,2,2-trifluoroethoxyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide

Rendimiento 98.1%

Disolventes

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was sealed
2. 2
   TemperaturaThe reaction mixture was then cooled to room temperature
3. 3
   FiltraciónThe mixture was filtered through a pad of celite
4. 4
   Lavadothe pad was rinsed with EtOAc (20 mL)
5. 5
   LavadoThe organic was washed with water (2×15 mL)
6. 6
   Secadodried (Na2SO4)
7. 7
   Concentraciónconcentrated
8. 8
   FiltraciónThe residue was then filtered through a pad of silica gel (30 g) with EtOAc/heptane (1:3)

Procedimiento

To a mixture of ethyl 2-oxocyclohexanecarboxylate (58.0 mg, 0.341 mmol), (R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (580 mg, 1.705 mmol), Cs2CO3 (1555 mg, 4.77 mmol), copper(I) iodide (32.5 mg, 0.170 mmol) was added 2,2,2-trifluoroethanol (871 μl, 11.93 mmol). The reaction was sealed and heated at 78° C. for 24 hours. LCMS indicated complete conversion to product. The reaction mixture was then cooled to room temperature and diluted with EtOAc (20 mL). The mixture was filtered through a pad of celite and the pad was rinsed with EtOAc (20 mL). The organic was washed with water (2×15 mL), dried (Na2SO4) and concentrated. The residue was then filtered through a pad of silica gel (30 g) with EtOAc/heptane (1:3) to give crude (R)—N—((S)-1-(2,5-difluoro-4-(2,2,2-trifluoroethoxyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide (0.601 g). LCMS (B) m/z 360.1 (M+H)+

Fuente