Reaction #1138

Reaction equation

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

Yield 76.4%

Solvents

DME

water

Water

ethyl acetate

Conditions

Workup

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

Procedure

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).

Source