Hydrochloric Acid → 2-(4-Bromobutoxy)tetrahydro-2H-pyran

Temperature

-20 °C

Methanesulfonyl chloride (20.3 ml.) is added slowly with stirring to a solution of 7-tetrahydropyranyloxyhept-2-yne-1-ol (52.5 g.) in 400 ml. of pyridine at -20° C. The mixture is stirred one hour at -20° C., and then is poured into a stirred mixture of 3-normal hydrochloric acid (1727 ml.) and 2,540 ml. of ice water. This mixture is extracted with diethyl ether. The extract is washed with cold one normal hydrochloric acid and then with saturated aqueous sodium chloride solution, dried, and evaporated at reduced pressure. The residue is dissolved in 500 ml. of dry acetone. Lithium bromide (26 g.) is added to the acetone solution, and the mixture is stirred and heated at reflux 1 hour, and then kept at 25° C. for 15 hours. The acetone is evaporated under reduced pressure, and the residue is extracted with diethyl ether. The diethyl ether extract is washed with water and then 3 times with saturated aqueous sodium chloride solution, dried, and evaporated. The residue is chromatographed on 3.5 kg. of silica gel, eluting with 24 l. of 10% ethyl acetate in Skellysolve B, collecting 1.5 l. fractions. Fractions 5-10 are combined and evaporated to give 25 g. of 1-bromo-7-tetrahydropyranyloxyhept-2-yne.

1. customat -20° C
2. extractionThis mixture is extracted with diethyl ether
3. washThe extract is washed with cold one normal hydrochloric acid
4. dry with materialwith saturated aqueous sodium chloride solution, dried
5. customevaporated at reduced pressure
6. dissolutionThe residue is dissolved in 500 ml
7. additionLithium bromide (26 g.) is added to the acetone solution
8. stirringthe mixture is stirred
9. temperatureheated
10. temperatureat reflux 1 hour
11. waitkept at 25° C. for 15 hours
12. customThe acetone is evaporated under reduced pressure
13. extractionthe residue is extracted with diethyl ether
14. extractionThe diethyl ether extract
15. washis washed with water
16. dry with material3 times with saturated aqueous sodium chloride solution, dried
17. customevaporated
18. customThe residue is chromatographed on 3.5 kg
19. washof silica gel, eluting with 24 l
20. customof 10% ethyl acetate in Skellysolve B, collecting 1.5 l
21. customevaporated
22. customto give 25 g

ORD record

ord-ffcb4c9936ce4ce887277304799e14d8

Source dataset

uspto-grants-1976_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US03974200