Chloromethyl Methyl Ether → (S)-4-Isopropyl-3-((S)-2-methoxymethyl-2-methyl-but-3-enoyl)-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-4-isopropyl-3-((E)-2-methyl-but-2-enoyl)-oxazolidin-2-one (prepared according to the method reported in Example 29c but using the opposite enantiomer of the oxazolidinone), (4.44 g, 21 mmol), in anhydrous toluene (40 mL) under nitrogen at −78° C. was added dropwise a solution of Sodium bis(trimethylsily)amide in toluene (0.6 M, 54 mL, 32 mmol). When addition was completed, the reaction mixture was left to stir at −78° C. for another minutes. Chloromethyl methyl ether (3.38 g, 42 mmol) was slowly added. Stirring was maintained at −60° C. for 30 minutes and then for 1 h as the temperature was allowed to rise to 0° C. Saturated ammonium chloride solution (230 mL) was added and the mixture was left to stir at room temperature for 10 minutes. The aqueous layer was extracted with ethyl acetate (2×) and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The crude residue was purified by silica gel chromatography using a Biotage KP-Sil 100 g cartridge eluting with a gradient of iso-hexanes/ethyl acetate 1:0 to 9:1 to give the title product (2.55 g, 48%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.80-1.00 (m, 6H), 1.50 (s, 3H), 2.25-2.45 (m, 1H), 3.35 (s, 3H), 3.46 (d, J=8.7 Hz, 1H), 4.16-4.23 (m, 2H), 4.28 (app t, J=8.2 Hz, 1H), 4.45-4.60 (m, 1H), 5.01 (d, J=17.6 Hz, 1H), 5.12 (d, J=10.7 Hz, 1H), 6.19 (dd, J=17.6, 10.7 Hz, 1H). LCMS (m/z) 255.3 [M+H], Tr=2.58 min.

Provenance & Evidence