Hydrochloric Acid → Hexahydrofuro(2,3-b)furan-3-ol

Temperature

37.5 °C

To the solution of Ethyl-2-(3-bromo-2-ethoxy tetra hydrofuran-3-yl)-2-oxoacetate in dichloromethane (V, 500 mL) as prepared in above example, sodium sulphite solution (225 g was dissolved in 1700 mL of water) was added at 25-35° C. Reaction mass was stirred for 5-8 hours at the same temperature and separated the organic and aqueous layers. Organic layer was washed with water (340 mL). Distilled out the solvent completely get ethyl-2-(2-ethoxy tetra hydrofuran-3-yl)-2-oxoacetate. Sodium borohydride (35.5 g) was dissolved in ethanol (400 mL) under nitrogen atmosphere, ethyl-2-(2-ethoxytetra hydrofuran-3-yl)-2-oxoacetate was dissolved in ethanol (100 mL) and slowly added to above solution at 15-30° C. Reaction mass was heated to 30-45° C., maintained for 5-8 hours, the reaction mass temperature was raised to 55° C. and stirred for 8 hours. The reaction mass was cooled to 20-30° C., ammonium chloride solution (115 g in 200 mL water) was slowly added and stirred for 1-2 hours. The reaction mass was filtered and filtrate was distilled out under vacuum to get residue. Dichloromethane (600 mL) was added to residue and cooled to −10° C. Hydrochloric acid (85 mL) was added slowly drop wise in 2 hours by maintaining temp −5 to 0° C., reaction mass was stirred for 60 minutes at −5 to 0° C. and distilled the solvent completely. The obtained residue was stripped out with isopropyl alcohol (2×200 mL, 1×100 mL), ethyl acetate (500 mL) was added to the resultant residue, stirred for 30-60 minutes and cooled to 10-15° C. The solution was filtered and filtrate was concentrated to get title compound IV (yield 56 g).

1. additionwas added at 25-35° C
2. customReaction mass
3. customseparated the organic and aqueous layers
4. washOrganic layer was washed with water (340 mL)
5. distillationDistilled out the solvent completely get ethyl-2-(2-ethoxy tetra hydrofuran-3-yl)-2-oxoacetate
6. dissolutionSodium borohydride (35.5 g) was dissolved in ethanol (400 mL) under nitrogen atmosphere
7. dissolutionethyl-2-(2-ethoxytetra hydrofuran-3-yl)-2-oxoacetate was dissolved in ethanol (100 mL)
8. additionslowly added to above solution at 15-30° C
9. customReaction mass
10. temperaturemaintained for 5-8 hours
11. temperaturethe reaction mass temperature was raised to 55° C.
12. stirringstirred for 8 hours
13. temperatureThe reaction mass was cooled to 20-30° C.
14. stirringstirred for 1-2 hours
15. filtrationThe reaction mass was filtered
16. distillationfiltrate was distilled out under vacuum
17. customto get residue
18. temperaturecooled to −10° C
19. temperatureby maintaining temp −5 to 0° C.
20. customreaction mass
21. stirringwas stirred for 60 minutes at −5 to 0° C.
22. distillationdistilled the solvent completely
23. additionwas added to the resultant residue
24. stirringstirred for 30-60 minutes
25. temperaturecooled to 10-15° C
26. filtrationThe solution was filtered
27. concentrationfiltrate was concentrated

ORD record

ord-4825f8f2eb5f4c49a85002d14da28fd2

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216990B2