| 摘要 |
<p>1474544 Cephalosporin cleavage process ELI LILLY & CO 12 June 1974 [18 June 1973] 26838/74 Heading C2C Process for cleaving the amic acid function of a compound of the Formula (I) in which R and R a are hydrogen, or R and R a taken together with the carbon atoms to which they are attached represent an ortho-phenylene ring; R 1 is a carboxy protecting group; and R 2 is hydrogen, acetoxy, methoxy, methylthio, (5 - methyl - 1,3,4 - thiadiazol - 2 - yl) - thio, or (1 - methyl - 1H - tetrazol - 5 - yl)thio; comprises (1) reacting the compound (I) with an alkyl chloroformate in the presence of a tertiary amine at a temperature in the range of from - 20‹ to +5‹ C. to form a mixed anhydride of Formula (II) in which R b is C 1-4 alkyl, and maintaining the temperature of (II) in the range of from - 20‹ to + 5‹ C.; (2) reacting the product (II) with up to one equivalent of a hydrazine of the formula R 3 HNNHR 4 , in which R 3 and R 4 independently are H or CH 3 , per equivalent of the 7-(amic acid)cephalosporin used in step (1), at a temperature in the range of from - 10‹ C. to room temperature; and (3) (a) reacting the reaction mixture with an acyl halide to produce the corresponding 7-acylamido cephalosporin; or (b) when at least one of R 3 and R 4 is CH 3 , recovering the corresponding 7-amino cephalosporin from the reaction mixture of the hydrazine treatment; or (c) when R 3 and R 4 are hydrogen, heating the reaction mixture from the hydrazine treatment to a temperature of from 50‹ to 100‹ C. to produce the corresponding 7-aminocephalosporin; or (d) when R 3 and R 4 are hydrogen, reacting the reaction mixture from the hydrazine treatment with acid to produce the 7-amino cephalosporin in the form of its acid addition salt.</p> |
