Sodium Hydroxide → 3-(5-Methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

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Reaction Steps

To a solution of 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-(2-tert-pentyloxycarbonylimino-2,3-dihydro-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (3.36 g.) in methanol (35 ml.) was added 1 N sodium hydroxide aqueous solution (5.5 ml.) under ice-cooling, and to the mixture was dropwise added an aqueous solution of sodium borohydride (91 mg.) in water (2.5 ml.) over 2 minutes at 10° to 15° C. The mixture was stirred for 10 minutes at the same temperature, and then methanol was distilled off from the mixture below 40° C. under reduced pressure. The remaining aqueous solution was washed with a small amount of ethyl acetate, adjusted to pH 5 to 6, with 10% hydrochloric acid, further washed with a small amount of ethyl acetate. The solution was adjusted to pH 2 with 10% hydrochloric acid, and then extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate and then treated with an activated charcoal. The solvent was distilled off from the extract till the volume of the extract became a small amount. The precipitates were collected by filtration, washed with a small amount of ethyl acetate, and then dried to give 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylimino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (1.69 g.). On the other hand, the mother liquor and the ethyl acetate washing were combined together and concentrated under reduced pressure, and then the precipitates were similarly treated as aforementioned to give the same object compound (0.80 g.).

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