Lithium Hexamethyldisilazide → (R)-4-benzyl-3-((R)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutanoyl)oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Under an inert atmosphere at -70° C. a solution of 4(R)-benzyl-3-isovaleroyl-oxazolidin-2-one (156.6 g) in tetrahydrofuran (500 ml) is added to a 1M lithium hexamethyldisilazide solution in tetrahydrofuran (600 ml, 0.60 mol) which has been diluted with anhydrous tetrahydrofuran (600 ml), and the batch is stirred for a further 75 minutes at -70° C. A solution of 4-methoxy-3-(3-methoxypropoxy)-benzyl bromide (145 g) in tetrahydrofuran (500 ml) is then added. The reaction temperature is allowed to rise from -70° C. to 0° C. over a period of 2 hours and the mixture is stirred at 0° C. for a further 18 hours. The reaction is quenched by the addition of a 10% aqueous ammonium chloride solution (250 ml) and the mixture is concentrated under reduced pressure and the aqueous phase is extracted with ethyl acetate (3×1.2 liters). The organic phases are washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. Purification of the residue by FC on silica gel (hexane/ethyl acetate 1:1) yields the title compound in the form of a white solid (202 g): m.p. 55°-56° C. (recrystallised from diethyl ether/hexane). Rf (ethyl acetate/hexane 1:2)=0.30. Anal. C27H35NO6 (469.58): calc. C, 69.06; H, 7.51; N, 2.98; found C, 68.64; H, 7.49; N, 3.12.

Provenance & Evidence