Ethyl Acetate → HCID 17985442, compound

Temperature

-78 °C

Add lithium diisopropylamine (0.454 mole) as a solution in tetrahydrofuran (100) mL to a solution of 3-furoic acid (23.36 g, 0.208 mole) at −78° C. over 30 minutes and stir for 1 hour at −78° C. To the resulting di-anion add 1,3-Bis-triisopropylsilanyloxy-propan-2-one as a solution in tetrahydrofuran (250 mL) over 30 minutes and stir at −78° C. for 1 hour and allow to warm to room temperature overnight. Quench the reaction with saturated aqueous ammonium chloride, pour into ethylacetate (1 L), add 1N HCL (1 L) and separate the two layers. Wash the organic layer with 1N HCl, water, and brine, dry over magnesium sulfate, filter and concentrate to an oil. Dissolve the crude oil in 50% tetrahydrofuran and 50% 3N HCl (1 L) and heat a reflux over night Distill off tetrahydrofuran, concentrate under reduced pressure and, add acetonitrile remove it under reduced pressure to azeotrope off the remaining water. Dissolve the resulting crude oil in acetonitrile (250 mL) and add the solution to a solution of toluene containing a catalytic amount of p-toluenesulfonic acid at reflux that is fitted with a Dean Stark trap over 30 minutes. Toluene was added to replace the acetonitrile and water removed by distillation and azetroping (500 mL). Heat the solution at reflux until it appears no further water is being removed. The hot solution was poured into an erlenmeyer flask and allowed to cool. Triturate the brown remaining residue with ethylacetate and methanol and combine it with the toluene solution and concentrate. Dilute with ethylacetate and wash with saturated aqueous sodium bicarbonate and brine, dry over magnesium sulfate and concentrate to an off white solid. Purification by flash chromatography eluting with hexane:ethylacetate gives 13.27 g (42%) of the title compound as a white solid.

1. stirringstir at −78° C. for 1 hour
2. temperatureto warm to room temperature overnight
3. customQuench
4. customthe reaction with saturated aqueous ammonium chloride
5. additionadd 1N HCL (1 L)
6. customseparate the two layers
7. washWash the organic layer with 1N HCl, water, and brine
8. dry with materialdry over magnesium sulfate
9. filtrationfilter
10. concentrationconcentrate to an oil
11. dissolutionDissolve the crude oil in 50% tetrahydrofuran
12. temperature50% 3N HCl (1 L) and heat
13. temperaturea reflux over night
14. distillationDistill off tetrahydrofuran
15. concentrationconcentrate under reduced pressure
16. additionadd acetonitrile
17. customremove it under reduced pressure
18. dissolutionDissolve the resulting crude oil in acetonitrile (250 mL)
19. additionadd the solution to a solution of toluene containing a catalytic amount of p-toluenesulfonic acid
20. temperatureat reflux that
21. customis fitted with a Dean Stark trap over 30 minutes
22. additionToluene was added
23. customremoved by distillation
24. temperatureHeat the solution
25. temperatureat reflux until it
26. customis being removed
27. additionThe hot solution was poured into an erlenmeyer flask
28. temperatureto cool
29. customTriturate the
30. concentrationconcentrate
31. additionDilute with ethylacetate
32. washwash with saturated aqueous sodium bicarbonate and brine
33. dry with materialdry over magnesium sulfate
34. concentrationconcentrate to an off white solid
35. customPurification by flash chromatography
36. washeluting with hexane

ORD record

ord-db18c328ff684e61ad6cfc2ce11226b5

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022065B2