Triethylamine → (S)-4-benzyl-3-[(2E)-3-(4-chlorophenyl)prop-2-enoyl]-1,3-oxazolidin-2-one

Temperature

-20 °C

An oven-dried, three-necked, 1 L 24/40 round-bottom flask equipped with a mechanical stirrer, a septum and a nitrogen inlet was charged with a solution of 20.00 g (0.110 mol) of 4-chlorocinnamic acid in 400 mL of anhydrous tetrahydrofuran. The reaction mixture was purged with nitrogen and stirred at −20° C. and then 19.93 mL (0.143 mol) of triethylamine and 14.84 mL (0.120 mol) of pivaloyl chloride were added via syringe. The reaction mixture was stirred at −20° C. for 30 min, then at room temperature for 1.5 h. A separate, oven-dried, three-necked, 2 L 24/40 round-bottom flask was equipped with a mechanical stirrer, and a nitrogen inlet. The contents were purged with nitrogen gas and then charged with 16.243 g (0.092 mol) of (S)-(−)-4-benzyl-2-oxazolidinone, 4.274 g (0.101 mol) of finely powdered anhydrous lithium chloride, 400 mL of anhydrous tetrahydrofuran and 16.61 mL (0.119 mol) of triethylamine. The reaction flask was fitted with an oven-dried fritted vacuum filtration funnel in one of its necks, and the reaction mixture was stirred at −20° C. The mixed anhydride prepared in the first reaction flask was separated from precipitated triethylamine hydrochloride by rapid filtration into the second flask with the aid of a slight vacuum applied to the filtration funnel. The reaction mixture in the second flask was again purged with nitrogen, stirred for 30 min at −20° C., then allowed to warm to room temperature and stirred an additional 5 h. At this point the reaction mixture was filtered again and concentrated in vacuo. The crystalline residue was dissolved in methylene chloride, washed with 0.5 M hydrochloric acid, water, saturated aqueous sodium bicarbonate, brine, then dried (MgSO4), filtered and evaporated. The residue was purified by rapid filtration through a six inch bed of silica gel 60 eluted with methylene chloride. Evaporation of the purified fractions and drying in vacuo afforded 23.38 g of the title compound.

1. customThe reaction mixture was purged with nitrogen
2. stirringThe reaction mixture was stirred at −20° C. for 30 min
3. customA separate, oven-dried
4. customthree-necked, 2 L 24/40 round-bottom flask was equipped with a mechanical stirrer, and a nitrogen inlet
5. customThe contents were purged with nitrogen gas
6. customThe reaction flask was fitted with an oven-dried fritted vacuum filtration funnel in one of its necks
7. stirringthe reaction mixture was stirred at −20° C
8. customwas separated
9. customfrom precipitated triethylamine hydrochloride
10. filtrationby rapid filtration into the second flask with the aid of a slight vacuum
11. customThe reaction mixture in the second flask was again purged with nitrogen
12. stirringstirred for 30 min at −20° C.
13. temperatureto warm to room temperature
14. stirringstirred an additional 5 h
15. filtrationAt this point the reaction mixture was filtered again
16. concentrationconcentrated in vacuo
17. dissolutionThe crystalline residue was dissolved in methylene chloride
18. washwashed with 0.5 M hydrochloric acid, water, saturated aqueous sodium bicarbonate, brine
19. dry with materialdried (MgSO4)
20. filtrationfiltered
21. customevaporated
22. filtrationThe residue was purified by rapid filtration through a six inch bed of silica gel 60
23. washeluted with methylene chloride
24. customEvaporation of the purified fractions
25. customdrying in vacuo

ORD record

ord-48b964ba58f4428aa0f1d5eadb229339

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07700778B2