N,O-bis(trimethylsilyl)acetamide → Benzhydryl 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-chloro-1-propen-1-yl]-3-cephem-4-carboxylate

Participants

Reaction Steps

To a stirred solution of XVIII (Z isomer) (20 g, 42 mmole) in CH2Cl2 (420 ml) containing N,O-bis(trimethylsilyl)acetamide (34 ml, 125 mmole) was added 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl chloride hydrochloride (15.2 g, 59 mmole) in three portions over a period of 30 minutes at -10° to 0° C. The mixture was stirred for 30 minutes at 0°-5° C. and concentrated under reduced pressure. The residual brown oil was dissolved in ethyl acetate (420 ml) and the solution was washed successively with saturated aqueous NaHCO3 (3×15 ml), saturated aqueous NaCl (15 ml), 10% HCl (15 ml) and saturated aqueous NaCl (15 ml), and concentrated to about 50 ml of the volume. To the concentrate was added n-heptane (200 ml) to give 28.5 g (90% pure) of the title compound VIII-1 (Z-isomer) as a colorless powder. M.p. >150° C. (dec.).

Provenance & Evidence