(5R)-3-(4-(1-benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3,5-difluorophenyl)-5-hydroxymethyloxazolidin-2-one → 5(R)-(3-Oxo-isoxazol-2-ylmethyl)-3-(4-(1-benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one

Participants

Reaction Steps

During the Mitsunobu reaction the ambident nucleophile 3-hydroxyisoxazole reacts with 5(R)-Hydroxymethyl-3-(4-(1-benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one to give a quantity of 5(R)-(3-Oxo-isoxazol-2-ylmethyl)-3-(4-(1-benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one. Failure to purify (e.g. by suitable column chromatography) the product from the Mitsunobu reaction described in GB99/01753 before subsequent reaction with 1-chloroethyl chloroformate and work-up using hydrochloric acid gives a quantity of 5(R)-(3-Oxo-isoxazol-2-ylmethyl)-3-(4-(1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one as the hydrochloride salt, which is identified in the mixture by correlation TOCSY NMR (TOtal Correlation SpectroscopY)— methylene carbon attached to the nitrogen of the isoxazolone ring has a shift of 48 ppm (characteristic of this linkage), and by LC-MS (MH+ 378-less chloride) using C-18 Hichrom RPB column, 5 mm, 25 cm×0.46 mm i.d; Eluant—650 ml Water, 350 ml Acetonitrile, 1 ml TFA (biograde); Flow—1.5 ml/min; Retention Times N-linked-Piperidene—Rt=2.0 min, O-linked Piperidene—Rt=3.25 min.

Provenance & Evidence