Sodium hydride → 5-(2,2-Dimethoxyethoxy)pent-1-yne

Temperature

40 °C

Pent-4-yn-1-ol (4.5 mL, 48 mmol) was dissolved in anhydrous THF (50 mL). Sodium hydride (60% w/w in mineral oil, 1.95 g, 49 mmol) was added portionwise over a 10 min period. The resulting slurry was heated at 40° C. for 30 min. and then allowed to cool to room temperature. 2-Bromoacetaldehyde dimethylacetal (5.67 mL, 48 mmol) was added and the reaction mixture was heated at 40° C. for 18 h, and it was quenched with water (2 mL). The resulting solution was concentrated and then partitioned between dichloromethane (2×100 mL) and 1N HCl (100 mL). The organic phases were then removed and washed with saturated NaHCO3 solution (100 mL), and saturated brine (100 mL); and then dried over sodium sulfate, filtered and concentrated in vacuo. The resulting crude product (2.91 g) was then chromatographed using a silica gel column and eluting under 10 psi of nitrogen pressure with dichloromethane; 2% v/v methanol in dichloromethane; and then 4% v/v methanol in dichloromethane. The appropriate fractions were combined and concentrated to give the title intermediate (2.78 g, 16.1 mmol, 33.5% yield—contained 0.5 molar equivalents of dichloromethane). NOTE: Due to the volatility of this intermediate, this compound should not be dried on a high vacuum line.

1. temperatureto cool to room temperature
2. temperaturethe reaction mixture was heated at 40° C. for 18 h
3. customit was quenched with water (2 mL)
4. concentrationThe resulting solution was concentrated
5. custompartitioned between dichloromethane (2×100 mL) and 1N HCl (100 mL)
6. customThe organic phases were then removed
7. washwashed with saturated NaHCO3 solution (100 mL), and saturated brine (100 mL)
8. dry with materialand then dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe resulting crude product (2.91 g) was then chromatographed
12. washeluting under 10 psi of nitrogen pressure with dichloromethane
13. concentrationconcentrated

ORD record

ord-f7a37f3af8d645bdad84f3b722780014

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080565B2