SU1041036A3 - Process for preparing 1-oxadethiacephalosporins - Google Patents

Abstract

PURPOSE:1-Oxadithiacephem cpds. I [ A is amino or protected amino; E is H or methoxy; Y is II(COB is carboxy or protected carboxy; X is H or nucleophile; Z is leaving gp.); the dotted line is alpha or beta-bond], e.g. 7alpha-benzamido3-methyl-1-dithia-1-oxa-3-cephem-4-carboxylic acid benzylester.

Description

00

This invention relates to a process for the preparation of novel 1-oxadiethiacephalosporins derivatives, which can be used as semi-products in the synthesis of 1-oxa antibiotics in children and acephalosporin. p yes A known method for the preparation of a 1-oxethylamine of a compound, namely, a biologically active 7 -W -, P-hydroxyphenyl; -carboxyacetamido - 7 |) (.- methoxy-3- (1-methyltetrazol-5-yl) -thiomethyl-l- occadeti-3-cepheme-4-carboxylic acid by removing the protective groups in the corresponding compound with the protected hydroxy and carboxy groups. The purpose of the invention is to obtain new intermediates in the synthesis of antibiotics of the 1-oxadethiacephalosporin group. Purpose. 1-oxadethiacephalosporins; the general formula is -tr -iryJ-CH2 5i (I) dooB 2) Ms C5H5YOKN. 0 KOCHj n. YL COOCH (SbH5) 2 to a solution of diphenylmethyl ester of 7o-benzamido-3-chloromethyl-3-chloro-1-dethia-1-oxacepham-4 (d-carboxylic acid (1.00 g) in dichloromethane (20 ml)) 1.18 n, a solution of chlorine S carbon tetrachloride (1.5 ets. To this mixture was added 1.89 and a solution of sodium methylate in methanol (3.8 eq.) over 5.5 mi at (-55) - ( -50) C. After stirring for 10 minutes, the mixture was acidified with acetic acid, stirred for 5 minutes, diluted with aqueous sodium bicarbonate solution, and extracted with dichloro methane. The extract was washed with water, dried, and evaporated to give diphenkmethyl th ester 7 | -benzamido-7o, -methoxy-3-chloromethyl-1-children-1HleijtM -l IlCONH 4-f® 2 (51 Y CHjCi de A is the free amino group or RCONH-, where R is free phenyl, phenyl , substituted with nitro, cyano, methyl, or chlorine, or benzyl; COOB — carboxyl, benzyloxycaronyl, diphenylmethoxycarbonyl, benzyloxycarbonyl, substituted by methyom or chlorine, or -naphthylmethoxycarbonyl, introduce the methoxy group; total form / V - m) CHjCl (JOOB where A and COOB have the above values, in excess astvora chlorine in carbon tetrachloride for 10 min - 2 h at O - (-54), followed by reacting the resulting mixture with an excess of alkali metal methylate in methanol for a time from 5 to 30 minutes at (-50) -. (-75) ° C and the selection of the target product by cracking with an organic solvent. Example.) AXIS, CfiHgCONH .Jo. oMyL% ci (1ооСн (СеН5) 2, -oxa-3-cephem-4-carboxylic acid. (0.52 g), .. 3430, 1787, 1682 cm H NMR: S CDCI-J 3.63S3H; 4.50S2H ; 4.55 S2E; 5.25 SlH; 7.00 SlH; 7.17, 95ml6H ..., in the same manner as described above, but replacing 1.89 n. Sodium methyl acetate in methanol (3.8 eq. ) by 2.00 n potassium methylate in methanol (5.0 eq.) and with stirring for 15 min, the same product was obtained (0.44 g). Similarly, in the fish in Table 1, other compounds of the formula L, 0 (; cTawn p I-H; WASON- | --G 1

Continued table. one.

Ph - eHitn Physical constants of compounds

: -table 2

Physical constants of 1-oxadethiacephalosporins of formula 1

Formula 1 are given in Table-2.

Claims (1)

METHOD FOR PRODUCING 1-OXADETHYCEPHALOSPORINS of the general formula boxyl, benzyloxycarbonyl, diphenylmethoxycarbonyl, benzyloxycarbonyl substituted with methyl or chlorine, or 'n-naphthylmethoxycarbonyl, characterized in that the compound; general formula SOOB where A and SOOB have the indicated values, they are subjected to 7-methoxylation and cleavage of hydrogen chloride in position 3 by processing its solution CH ₈ C1, where A is a free amino group, go RC0NH-, where R is free phenyl, phenyl substituted with nitro, cyano, methyl or chlorine, or benzyl; СООВ - carv dichloromethane with an excess of a solution of chlorine in carbon tetrachloride for 10 min –2 h at 0 - (-54) ° С followed by interaction of the resulting mixture with an excess of alkali metal methylate in methanol for 5-30 min at (-50) - (-75) ° C and the selection of the target product by extraction with an organic solvent.