Triethylamine → (S)-3-cyclohexylpropionyl-4-isopropyloxazolidin-2-one

Temperature

0 °C

A solution of 3-cyclohexylpropanoic acid (9.49 g, 60.7 mmol) in THF (100 mL) was cooled to −78° C. in a cooling bath and then treated with triethylamine (15.14 mL, 108 mmol) and pivaloyl chloride (11.6 mL, 94 mmol) to provide “Mixture A.” The cooling bath was removed and Mixture A was stirred at 0° for 1 hour. A solution of 4-(S)-isopropylisoxazolidinone (10.55 g, 81.7 mmol) in THF (100 mL) was cooled to −45° C. and then treated with butyllithium (51.1 mL of a 1.6M hexane solution), forming a thick slurry as “Mixture B.” Mixture B was allowed to warm to 0° C. over 1 hour. Mixture A was cooled to −78° C. and then Mixture B was added to the Mixture A. The cooling bath was removed and the combine mixture was permitted to warm to ambient temperature. The mixture remained at ambient temperature for 1 hour and then was diluted with 0.25 M hydrochloric acid (200 mL). The dilution was extracted with ethyl acetate (200 mL) and the extract was washed with saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL), dried over MgSO4, filtered, and evaporated to dryness. Product was purified from the residue by chromatography on silica gel, using 0-20% ethyl acetate/hexane as eluent to provide (S)-3-cyclohexylpropionyl-4-isopropyloxazolidin-2-one (17.2 g). MS (M+1): 268.

1. customto provide “Mixture A
2. custom” The cooling bath was removed
3. customforming a thick slurry as “Mixture B
4. temperatureMixture A was cooled to −78° C.
5. additionMixture B was added to the Mixture A
6. customThe cooling bath was removed
7. temperatureto warm to ambient temperature
8. waitThe mixture remained at ambient temperature for 1 hour
9. additionwas diluted with 0.25 M hydrochloric acid (200 mL)
10. extractionThe dilution was extracted with ethyl acetate (200 mL)
11. washthe extract was washed with saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL)
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. customevaporated to dryness
15. customProduct was purified from the residue by chromatography on silica gel

ORD record

ord-41c3d981da6d4d258e5442e26b3b8179

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06525036B2