Diisopropylamine → 3-(1-Oxo-2-(S)-(((phenylmethyl)thio)methyl)butyl)-4-(S)-(1-methylethyl)-2-oxazolidinone

A solution of the N-acylated product of Step 6 (36.9 g, 185 mmol) in anhydrous THF (70 mL) was added to a magnetically stirred, cooled (-78° C.) solution of LDA (lithium diisopropylamide) (prepared from 28.6 mL (20.6 g, 204 mmol) of diisopropylamine and 127.5 mL (1.6M in hexane, 204 mmol) of n-butyllithium) in anhydrous THF (240 mL). After stirring for 0.5 h at -78° C. the resultant lithium enolate was treated with benzyl bromomethyl sulfide (52.3 g, 241 mmol) for 2 h at -20° C. The reaction was quenched by the addition of half-saturated aq NH4Cl (200 mL). Volatiles were removed in vacuo and the product was extracted into CH2Cl2 (3×). The combined organic extracts were successively washed with 1 M aqueous sodium bisulfate (2×), 1M aqueous KHCO3 (2×) and brine, dried over MgSO4 and concentrated in vacuo to give 76.5 g of a yellow liquid. This crude material was roughly purified by flash chromatography on silica with EtOAc:hexane 1:99, 2:98, 5:95, 10:90 and 15:85 to give the title compound as a colorless liquid (48.9 g), which was used as such for the next step.

1. customThe reaction was quenched by the addition of half-saturated aq NH4Cl (200 mL)
2. customVolatiles were removed in vacuo
3. extractionthe product was extracted into CH2Cl2 (3×)
4. washThe combined organic extracts were successively washed with 1 M aqueous sodium bisulfate (2×), 1M aqueous KHCO3 (2×) and brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo

ORD record

ord-550cf2db1df0488f9fea98436c7b7541

Source dataset

uspto-grants-1999_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05856322