2,2,6,6-Tetramethylpiperidine → 2-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-mesyloxy-prop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Participants

Reaction Conditions

Reaction Steps

A 1.6M solution of butyllithium in hexane (10.3 cc) is added, in the course of 10 minutes, to a solution of 2,2,6,6-tetramethylpiperidine (2.33 g) in tetrahydrofuran (15 cc) at 20° C. The mixture is stirred for 20 minutes at 20° C. and then cooled to -70° C. A solution of 3-acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (7.61 g) in tetrahydrofuran (20 cc) is then added in the course of 15 minutes. The mixture is stirred for a further 20 minutes at -70° C. and hexamethylphosphorotriamide (15 cc) is then added in the course of 3 minutes, followed by a solution of methanesulphonyl chloride (4.5 cc) in tetrahydrofuran (10 cc) in the course of 3 minutes. The mixture is stirred for 45 minutes at -70° C., the temperature is then left to rise to 0° C. and the mixture is diluted with ethyl acetate (300 cc). The solution is washed successively with a saturated solution of sodium bicarbonate (100 cc) and distilled water (100 cc), dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.20) (150 g) (diameter of the column: 3.7 cm; height: 30 cm). Elution is carried out with a 22/78 (by volume) ethyl acetate/cyclohexane mixture (2.5 liters), 100 cc fractions being collected. Fractions 12 to 20 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the Z form of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-mesyloxy-prop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (3.2 g) in the form of a hard, pale yellow foam.

Provenance & Evidence