Methyl triflate → O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(1-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioate

Participants

Reaction Steps

To a solution of 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (6.00 g: 5.87 mMol.) in a mixture of dichloromethane (60 ml) and tetrahydrofuran (30 ml) is added at -50° C. diisopropylethylamine (1.12 g: 6.43 mMol.). After stirring at -40°--50° C. for 3 minutes, trifluoromethanesulfonic acid methyl ester (0.73 ml: 6.45 mMol.) is added to the mixture. After stirring at the same temperature for 30 minutes, the reaction mixture is quenched with 10% hydrochloric acid (2.4 ml), diluted with water, and extracted with ethyl acetate. The extract is washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel chromatography (toluene: ethyl acetate=3:2) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(3-methyl-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester [1.84 g: Yield: 30%. NMR δ(CDCl3 -CD3OD) ppm: 1.52(s, 9H), 3.43, 3.55(ABq, J=17.3 Hz, 2H), 3.87, 3.94(ABq, J=13.7 Hz, 2H), 3.95(s, 3H), 5.12 (d, J=4.8 Hz, 1H), 5.99 (d, J=4.8 Hz, 1H), 6.96 (s, 1H), 7.06(s, 1H), 7.15-7.50(m, 25H), 7.73(s, 1H). IR ν(CHCl3) cm-1: 3398, 3300, 1784, 1714, 1683, 1540, 1490, 1443, 1366, 1277, 1220, 1153, 1114, 1077, 970, 910.], 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(1-methyl-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (2.71 g: Yield: 46%), and 7β-[(Z)-2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-trityloxyiminoacetamido]-3-(2-methyl-1,2,3-triazol-4-yl)-thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (0.51 g: Yield: 8%).

Provenance & Evidence