Reacción #1138

Ecuación de reacción

5-bromo-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine

triphenylphosphine

potassium carbonate

2-methyl-3-butyn-2-ol

→

5-(2-hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine

Rendimiento 76.4%

Disolventes

DME

water

Water

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe reaction flask was heated at 80° C. for 18 h
2. 2
   Filtraciónthis was filtered through celite
3. 3
   OtroThe organic phase was separated
4. 4
   Extracciónthe aqueous layer extracted with ethyl acetate (3×20 mL)
5. 5
   Lavadothe combined ethyl acetate extracts were washed with brine (20 mL)
6. 6
   Secadodried (MgSO4)
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   OtroThe crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants

Procedimiento

A mixture of 5-bromo-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine (1 g, 3.06 mmol), 10% palladium on charcoal (80 mg, 0.077 mmol), copper(I)iodide (58 mg, 0.30 mmol), triphenylphosphine (80 mg, 0.30 mmol) and potassium carbonate (1.06 g, 7.65 mmol) in DME (5 mL) and water (5 mL) was stirred at 25° C. After 0.75 h 2-methyl-3-butyn-2-ol (0.74 mL, 7.65 mmol) was added and the reaction flask was heated at 80° C. for 18 h. Water (30 mL) and ethyl acetate (30 mL) were added to the cooled mixture and this was filtered through celite. The organic phase was separated and the aqueous layer extracted with ethyl acetate (3×20 mL) and the combined ethyl acetate extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants to afford 5-(2-hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine as an oil (772 mg, 76%). LRMS (EI) m/e 231 (M+ +H --CO2 and isobutylene), 230 (M+ --CO2 and isobutylene), 229 (M+ --CO2 tBu); 1H NMR (CDCl3, 300 MHz): δ 8.56 (b-s, 1H), 8.37 (b-d, J=1.5 Hz, 1H), 7.53 (m, 1H), 4.93 (b-m, 0.5H), 4.76 (b-m, 0.5H), 3.5-3.7 (b-m, 2H), 2.36 (m, 1H), 1.75-2.0 (b-m, 3H), 1.72 (b-s, 1H), 1.63 (s, 6H), 1.45 (b-s, 3H), 1.21 (b-s, 6H).

Fuente