Tributylphosphine → (5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one

Participants

Reaction Steps

3-(4-Imidazol-1-yl-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (693 mg, 2.5 mM, see WO 96-23788) and 3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole (649 mg, 2.5 mM) were suspended by stirring in dry tetrahydrofuran (25 ml) under nitrogen in an ice-bath. Tributylphosphine (808 mg, 4 mM) was added followed by 1,1′-(azodicarbonyl)dipiperidine (945 mg, 3.75 mM) dissolved in tetrahydrofuran (10 ml) over 10 minutes. The mixture was then stirred 18 hours, allowing the temperature to rise to ambient, then filtered, and the filter cake washed with tetrahydrofuran. The combined filtrates were evaporated and the residue purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined, evaporated, and the residue triturated with diethyl ether to give the desired product (1.36 g), contaminated with tributylphosphine oxide. NMR (DMSO-d6) δ: 3.95 (dd, 1H); 4.16 (dd, 1H); 4.26 (t, 1H); 4.41 (dd, 1H); 4.99 (dd, 1H); 5.08 (dd overlapping m, 2H); 6.89 (d, 1H); 7.10 (t, 1H); 7.44 (dd, 1H); 7.52 (d, 1H); 7.66 (t, 1H); 7.71 (dd, 1H); 7.98 (m, 1H); 8.90 (d, 1H). MS (ESP): 518 (MH+) for C19H15Cl3FN5O5

Provenance & Evidence