公开(公告)号：US3708477A

公开(公告)日：1973-01-02

申请号：US3708477D

申请日：1970-10-16

Applicant: ROUSSEL UCLAF

Inventor： MARTEL J ,  HEYMES R

IPC: A22B5/16 ,  C07D207/34 ,  C07D207/36 ,  C07D207/38 ,  C07D271/04 ,  C07D501/08 ,  C07D513/04 ,  F21V17/16 ,  G09F9/00 ,  H01H9/18 ,  H01H13/52 ,  C07D99/24

CPC classification number: F21V17/16 ,  C07D207/34 ,  C07D207/36 ,  C07D207/38 ,  C07D271/04 ,  C07D501/08 ,  C07D501/18 ,  C07D501/38 ,  C07D501/42 ,  C07D501/46 ,  C07D513/04 ,  G09F9/00

Abstract: PROCESS FOR THE PREPARATION OF RACEMIC OR OPTICALLYACTIVE CEPHALOSPORINE DERIVATIVES OF THE FORMULA

2,3-(-CO-N(-R1)-CH2-),7-NH2-2-CEPHEM

WHEREIN R1 IS A MEMBER SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL, SUBSTITUTED AKYL, ARYL AND SUBSTITUTED ARYL, WHICH COMPRISES THE STEPS OF REACTING AN AMINO ACID OF THE FORMULA

R1-NH-CH2-CH2-COOH

WITH BENZYL ALCOHOL, CONDENSING THE BENZYL ESTER THUS OBTAINED WITH AN OXALATE, CONVERTING THE BENZYL ESTER OF 2,3DIOXI-4-CARBOXY-PYRROLIDINE INTO THE CORRESPONDING ACID, SUBJECTING SAID ACID TO AMINOMETHYLATION, THUS YIELDING A COMPOUND OF THE FORMULA

1-R1,3-OH,4-(R"-N(-R'')-CH2-)PYRROL-3-IN-2-ONE

CONVERTING SAID COMPOUND INTO THE CORRESPONDING 4-ACYLTHIOMETHYL DERIVATIVE, CONVERTING SAID DERIVATIVE INTO THE CORRESPONDING 4-THIOMETHYL DERIVATIVE, CONDENSING SAID DERIVATIVE WITH AN ENAMINE OF THE FORMULA

R-OOC-C(-Y)=CH-NH2

TO OBTAIN A THIAZINE DERIVATIVE OF THE FORMULA

2-(Y-CH(-COO-R)-),5-R1-2,3,4,5,6,7-HEXAHYDRO-PYRROLO

(3,4-D)-1,3-THIAZIN-4-ONE

CONVERTING SAID THIAZINE DERIVATIVE INTO A COMPOUND OF THE FORMULA

2-(H2N-CH(-COOH)-),5-R1-2,3,4,5,6,7-HEXAHYDRO-PYRROLO

(3,4-)-1,3-THIAZIN-4-ONE

SUBJECTING SAID COMPOUND TO THE ACTION OF A TRITYLATION AGENT, RECOVERING THE THREO ISOMER OF THE TRITYLATED DERIVATIVE, LACTAMIZING SAID THREO ISOMER TO OBTAIN THE Y-LACTAM OF DL-6H,7H-CIS-7-TRITYLAMINO-3-AMINOALKYL-CEPH 3-EME-4-CARBOXYLIC ACID, DETRITYLATING SAID Y-LACTAM AND RECOVERING SAID RACEMIC OF OPTICALLY ACTIVE CEPHALOSPORIN DERIVATIVES. THESE COMPOUNDS ARE USEFUL AS INTERMEDIATES IN THE PREPARATION OF THE CORRESPONDING 7ACYLAMINO DERIVATIVES OF THE FORMULA

2,3-(-CO-N(-R1)-CH2-),7-(R2-NH-)-2-CEPHEM

WHEREIN R1 HAS THE ABOVE DEFINITION AND R2 IS THE ACYL OF AN ORGANIC CARBOXYLIC ACID WHICH COMPOUNDS ARE ALSO PART OF THE INVENTION AND ARE USEFUL AS ANTIBIOTICS.