Triethylamine → (S)-4-benzyl-3-(4-cyclohexylbutanoyl)oxazolidin-2-one

Temperature

-78 °C

A solution of pivaloyl chloride (3.57 g, 2.96 mmol) in THF (25 ml) was added to a cold (-78° C.) solution of 4-cyclohexylbutyric acid (5.042 g, 29.62 mmol) and triethyl amine (3.60 g, 35.6 mmol) in THF (100 mL). The resultant white suspension was stirred for 10 min. at -78° C. and then warmed to 0° C. and kept there for 30 min. The reaction mixture was recooled to -78° C. and a cold (-78° C.) metallated oxazolidinone solution in THF (125 ml) [prepared by the addition of n-BuLi (17.65 ml. of 1.65M solution in hexane, 28.2 mmol) to a -78° C. solution of (S)-4-(phenylmethyl)-2-oxazolidinone in THF (125 ml)] was added via a cannula under the positive pressure of argon. The reaction mixture was then warmed to 0° C. and kept there for another 30 min. The reaction was quenched by the addition of saturated NH4Cl (75 ml). The volatiles were removed on rotavapor at reduced pressure and the residue was extracted with CH2Cl2 (3×200 ml). The combined organic phases were washed with 1N NaOH (150 ml) and dried (Na2SO4). The organic layer was concentrated and the residue was purified by flash silica gel chromatography, eluting with hexane:ethyl acetate (3:1) to yield 8.066 g (85%) of (S)-3-(4-cyclohexyl-1-oxobutyl)-4-(phenylmethyl)-2-oxazolidinone: Rf 0.34 (3:1 hexane:ethyl acetate), m.p. 69°-70° C. [α]D25 +47.3° (c 0.97 CHCl3).

1. temperaturewarmed to 0° C.
2. waitkept there for 30 min
3. customwas recooled to -78° C.
4. customa cold (-78° C.)
5. additionwas added via a cannula under the positive pressure of argon
6. temperatureThe reaction mixture was then warmed to 0° C.
7. waitkept there for another 30 min
8. customThe reaction was quenched by the addition of saturated NH4Cl (75 ml)
9. customThe volatiles were removed on rotavapor at reduced pressure
10. extractionthe residue was extracted with CH2Cl2 (3×200 ml)
11. washThe combined organic phases were washed with 1N NaOH (150 ml)
12. dry with materialdried (Na2SO4)
13. concentrationThe organic layer was concentrated
14. customthe residue was purified by flash silica gel chromatography
15. washeluting with hexane:ethyl acetate (3:1)

ORD record

ord-7a2256a9976e4946811dc0cd037f65ed

Source dataset

uspto-grants-1992_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05128448