Diisopropylamine → (4S, 5R)-3-[(2S)-1-oxo-2-((benzylthio)methyl)-4-methylpentyl]-4-methyl-5-phenyl-2-oxazolidinone

Temperature

-78 °C

A solution of lithium diisopropylamide was prepared from 1.96 mL (1.42 g) of diisopropylamine and 7.6 mL of n-butyllithium (1.75M in hexane) in 14 mL of THF. The solution was cooled to -78° C. with stirring, combined with a solution of (4S, 5R)-3-(1-oxo-4-methylpentyl)-4-methyl-5-phenyl-2-oxazolidinone (3.50 g) in THF (14 mL) and stirred for 30 min at -78° C. To this mixture was added 2.1 mL (3.1 g) of benzyl bromomethyl sulfide. The reaction mixture was stirred for 2 h at -25° C. and for 2 h at 0° C. Aqueous NH4Cl solution was added to the mixture. The organic solvents were removed in vacuo and the residue was extracted twice with CH2Cl2. The combined organic extract was washed twice with 1M aqueous NaHSO4, then with saturated NaHCO3, brine, dried over Na2SO4 and evaporated. The residue was subjected to flash chromatography on silica gel (hexane-EtOAc) to give 5.0 g (96% yield) of (4S, 5R)-3-[(2S)-1-oxo-2-((benzylthio)methyl)-4-methylpentyl]-4-methyl-5-phenyl-2-oxazolidinone as a clear oil. Characteristic analytical data are as follows: 1H NMR (300 MHz, CDCl3) δ7.24-7.47 (m, 10H), 5.66 (d, J=7 Hz, 1H), 4.81 (p, J= 7 Hz, 1H), 4.31-4.36 (m, 1H), 3.80 (AB q, J=13 Hz, 2H), 2.72 (dd, J=9, 14 Hz, 1H), 2.52 (dd, J=5, 14 Hz, 1H), 1.35-1.71 (m, 3H), 0.89-0.95 (m, 9H); [α]25D -91° (c=2.60, CH2Cl2)

1. stirringstirred for 30 min at -78° C
2. stirringThe reaction mixture was stirred for 2 h at -25° C. and for 2 h at 0° C
3. customThe organic solvents were removed in vacuo
4. extractionthe residue was extracted twice with CH2Cl2
5. extractionThe combined organic extract
6. washwas washed twice with 1M aqueous NaHSO4
7. dry with materialwith saturated NaHCO3, brine, dried over Na2SO4
8. customevaporated

ORD record

ord-9c927322d1764a24a7d5fc095e4d1972

Source dataset

uspto-grants-1995_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05470834