Propargyl alcohol → ({4-[(Prop-2-yn-1-yl)oxy]butoxy}methyl)benzene

Temperature

40 °C

To a 1:1 mixture of propargyl alcohol (100 mL, 1.72 mol) and anhydrous THF (100 mL) was added sodium hydride (60% w/w dispersion in mineral oil, 14.0 g, 0.35 mol) under nitrogen, portionwise, over 30-35 min. An second reaction mixture was prepared in essentially the same manner. Both reaction mixtures were heated at 40° C. for 2 h and then cooled to room temperature. 4-Benzyloxy-1-bromobutane (90%, 35.0 g, 0.137 mol) was added to each reaction mixture. The resulting solutions were heated at 40° C. for 22 h and then quenched with water (˜5 mL), combined and concentrated in vacuo. The resulting crude product was then partitioned between dichloromethane (2×300 mL) and water (200 mL). The organic phases were removed, washed with saturated brine (150 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude title intermediate (67 g) as a yellow oil. This oil was then chromatographed on a silica gel column (˜8 kg, 230-400 mesh, flash under 10 psi nitrogen pressure) eluting with dichloromethane (Rf=0.45, dichloromethane). The appropriate fractions were combined and concentrated to give the title intermediate as a clear oil (37.2 g, 0.17 mol, 62% yield).

1. customAn second reaction mixture
2. customwas prepared in essentially the same manner
3. customBoth reaction mixtures
4. temperaturecooled to room temperature
5. temperatureThe resulting solutions were heated at 40° C. for 22 h
6. customquenched with water (˜5 mL)
7. concentrationconcentrated in vacuo
8. customThe resulting crude product was then partitioned between dichloromethane (2×300 mL) and water (200 mL)
9. customThe organic phases were removed
10. washwashed with saturated brine (150 mL)
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto afford the crude title intermediate (67 g) as a yellow oil
15. customThis oil was then chromatographed on a silica gel column (˜8 kg, 230-400 mesh, flash under 10 psi nitrogen pressure)
16. washeluting with dichloromethane (Rf=0.45, dichloromethane)
17. concentrationconcentrated

ORD record

ord-4a8eee1fc0a7460b8b44f3fd70648b19

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080565B2