Hexane → (S)-(+)-4-Isopropyl-3-propionyl-2-oxazolidinone

Temperature

-78 °C

To a cooled solution (-78° C.) of 1.5910 g (12.316 mmole of (+)-(4S)-3-(1-oxopropyl)-4-(1-methylethyl)-2-oxoazolidinone (A) in 20 ml of THF under N2 atmosphere is added 5.80 ml of 2.32M n-BuLi in hexane (13.55 mmole, 1.1 equiv.) to form the conjugate base. The milky slurry is stirred for 1 hour before 1.11 ml (1.1852 g, 12.81 mmoles, 1.04 equiv., mwt 92.53, bp 77°-9° C., d 1.065) of propionyl chloride is added in one portion. The slurry dissolves instantly to a clear orange solution. After stirring an additional 15 min. at -78° C., the reaction is quenched with 20 ml sat. NH4Cl, and the THF is removed in vacuo at RT (room temp). The resultant concentrate is taken up in ether and extracted successively with aq. NaHCO3, water, brine and dried over anh. Na2SO4. Evaporation of the solvent followed by flash chromatography affords 1.82 g (80%) of purified product B as a viscous yellow oil. Proton NMR (200 MHz) in CDCl3 shows: ##STR58## 4.41 (d of t, 1H, J=7.6 Hz, J=3.6 Hz, C3 -H); 4.22 (m, 2H, 2J=5.4 Hz, C4 -H); 2.92 (q of d, 2H, J=7.7 Hz, J=4.0 Hz, C9 -H); 2.35 (m, 1H, J=7.0 Hz, J=3.9 Hz, C2 -H); 1.14 (t, 3H, J=7.7 Hz, C10 -H); 0.89, 0.85 (d, 6H, J=7.0 Hz, C1 -H).

1. customto form the conjugate base
2. additionis added in one portion
3. dissolutionThe slurry dissolves instantly to a clear orange solution
4. customthe reaction is quenched with 20 ml sat. NH4Cl
5. customthe THF is removed in vacuo at RT (room temp)
6. concentrationThe resultant concentrate
7. extractionextracted successively with aq. NaHCO3, water, brine
8. dry with materialdried over anh. Na2SO4
9. customEvaporation of the solvent

ORD record

ord-85b6026145b54a91b23a859c9e2a7e5d

Source dataset

uspto-grants-1988_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04791207