Tributylphosphine → (5S)-3-(3-fluoro-4-morpholino-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one

Participants

Reaction Steps

To a stirred solution of 3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole (260 mg, 1.0 mmol), 5(R)-hydroxymethyl-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one (see WO 95/07271; 293 mg, 1 mmol) and tributylphosphine (303 mg, 1.5 mmol) in dry tetrahydrofuran (10 ml) at 0° C. under a nitrogen atmosphere, was added 1,1′-(azodicarbonyl)dipiperidine (378.5 mg, 1.5 mmol) in dry tetrahydrofuran (3 ml). The reaction allowed to warm to room temperature and was stirred for 4 days by which time a white suspension had formed. The reaction mixture was filtered and the residue washed with tetrahydrofuran. The filtrate was reconcentrated by rotary evaporation to give a yellow oil (1.2 g) which was purified by MPLC (30% ethyl acetate/hexane, ICN Alumina N 32-63) and further MPLC (100% CH2Cl2, ICN Alumina N 32-63). Concentration of the fractions by rotary evaporation gave the title compound as a crisp white foam (296 mg, 55%). NMR: 2.97 (t, 4H), 3.73 (t, 4H), 3.88 (m, 1H), 4.17 (m, 2H), 4.38 (m, 1H), 5.04 (m, 3H), 6.90 (s, 1H), 7.06 (t, 1H), 7.18(dd, 1H), 7.46 (dd, 1H), 8.91 (d, 1H); m/z ES+ (M+H)=537.

Provenance & Evidence