p-Toluenesulfonic acid → (R)-(+)-3-Chlorostyrene oxide

Temperature

70 °C

Into toluene (1,000 ml) were added (R)-3-chloromandelic acid (10 g) and p-toluenesulfonic acid (0.2 g), and the resulting mixture was stirred at 70° C. for 2 hours. The solvent was distilled off under reduced pressure. To the residue were added toluene (100 ml) and then, under ice-cooling and dropwise, 3,4-dihydro-2H-pyran (5.0 g), and the resulting mixture was stirred at the same temperature for 1 hour. The reaction mixture was washed with a saturated aqueous sodium hydrogen carbonate solution, then the organic layer was further washed with a saturated aqueous sodium chloride solution and dried with anhydrous magnesium sulfate. The desiccant was filtered off and then a 70% sodium dihydrobis(2-methoxyethoxy)aluminate toluene solution (16.7 g) was dropwise added to the filtrate with ice-cooling. The resulting mixture was stirred at the same temperature for 1 hour. The reaction mixture was added into a 30% aqueous (+)−potassium sodium tartrate solution (60.0 g), stirred for 1 hour and then the organic layer was separated. The organic layer obtained was washed with water and further with a saturated aqueous sodium chloride solution and then dried with anhydrous magnesium sulfate. The desiccant was filtered off. Then, to the filtrate were added triethylamine (10.8 g) and, under ice-cooling and dropwise, methanesulfonyl chloride (6.42 g). The resulting mixture was stirred at the same temperature for 1 hour, the reaction mixture was washed with water, then methanol (20 ml) and p-toluenesulfonic acid (10.4 g) were added thereto, and the resulting mixture was stirred at 50° C. for 1 hour. The reaction mixture was washed with water, then a 20% aqueous NaOH solution (40 g) was added thereto under ice-cooling, and the resulting mixture was stirred at the same temperature for 2 hours. The reaction mixture was washed with water, further the organic layer was washed with a saturated aqueous sodium chloride solution and dried with anhydrous magnesium sulfate. The desiccant was filtered off, then the solvent was distilled off under reduced pressure, and the resulting oily substance was distilled under reduced pressure to obtain a colorless oily compound mentioned above (6.6 g, yield 79.7%). The optical purity of the product obtained was 99.9% e.e. as determined by HPLC.

1. distillationThe solvent was distilled off under reduced pressure
2. additionTo the residue were added toluene (100 ml)
3. temperatureunder ice-cooling
4. stirringdropwise, 3,4-dihydro-2H-pyran (5.0 g), and the resulting mixture was stirred at the same temperature for 1 hour
5. washThe reaction mixture was washed with a saturated aqueous sodium hydrogen carbonate solution
6. washthe organic layer was further washed with a saturated aqueous sodium chloride solution
7. dry with materialdried with anhydrous magnesium sulfate
8. filtrationThe desiccant was filtered off
9. additiona 70% sodium dihydrobis(2-methoxyethoxy)aluminate toluene solution (16.7 g) was dropwise added to the filtrate with ice-
10. temperaturecooling
11. stirringThe resulting mixture was stirred at the same temperature for 1 hour
12. additionThe reaction mixture was added into a 30% aqueous (+)−potassium sodium tartrate solution (60.0 g)
13. stirringstirred for 1 hour
14. customthe organic layer was separated
15. customThe organic layer obtained
16. washwas washed with water and further with a saturated aqueous sodium chloride solution
17. dry with materialdried with anhydrous magnesium sulfate
18. filtrationThe desiccant was filtered off
19. additionThen, to the filtrate were added triethylamine (10.8 g)
20. temperatureunder ice-cooling
21. stirringThe resulting mixture was stirred at the same temperature for 1 hour
22. washthe reaction mixture was washed with water
23. additionmethanol (20 ml) and p-toluenesulfonic acid (10.4 g) were added
24. stirringthe resulting mixture was stirred at 50° C. for 1 hour
25. washThe reaction mixture was washed with water
26. additiona 20% aqueous NaOH solution (40 g) was added
27. temperatureunder ice-cooling
28. stirringthe resulting mixture was stirred at the same temperature for 2 hours
29. washThe reaction mixture was washed with water
30. washfurther the organic layer was washed with a saturated aqueous sodium chloride solution
31. dry with materialdried with anhydrous magnesium sulfate
32. filtrationThe desiccant was filtered off
33. distillationthe solvent was distilled off under reduced pressure
34. distillationthe resulting oily substance was distilled under reduced pressure
35. customto obtain a colorless oily compound
36. customThe optical purity of the product obtained

ORD record

ord-8d3386f294474eb8ac8d9c49bf82e07d

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06642395B1