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

ORD record

ord-af623586e2db4b39a010b537364f7f3d

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07491716B2