Lithium Hexamethyldisilazide → (4R,5S)-3-[(R)-3-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-3-hydroxy-pentanoyl]-4,5-diphenyl-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A 10 ml round bottomed flask was charged with 389.4 μL lithium bis(trimethylsilyl)amide solution (1.0 M in THF, 0.385 mmol, 1.1 eq) and the solution was cooled to −78° C. 108.4 mg (4R,5S)-3-acetyl-4,5-diphenyl-oxazolidin-2-one (0.385 mmol, 1.1 eq), as obtainable from Example 8, in 650 μL THF were slowly added (addition time: 5 min). During the addition, the color changed from colorless to bright yellow. After 2 h at −78° C., the solution was cooled to −95° C. and 100.0 mg 1-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-propan-1-one (0.350 mmol), as obtainable from Example 7, dissolved in 400 μL THF were slowly added (addition time: 5 min). The solution was kept for additional 30 min at −95° C. and then for 45 min at −78° C. Subsequently, the reaction was quenched by addition of 5 mL aqueous 0.5 M HCl. The mixture was extracted three times with 10 mL, in total 30 mL dichloromethane and the combined extracts were dried over 1 g sodium sulfate (30 min) and filtered. The filter cake was washed with 2 mL dichloromethane. After removal of solvent in a rotary evaporator (40° C., 5 mbar), the title compound was obtained as a colorless oil (206.7 mg, 104% by weight, dr=92:8 (1H-NMR).

Provenance & Evidence