Reaktion #1138

Reaktionsgleichung

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

Ausbeute 76.4%

Lösungsmittel

DME

water

Water

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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).

Quelle