Process for preparing 2-amino-5-cyanobenzoic acid derivatives
View Patent ↗Disclosed is a method for preparing a compound of Formula 1 comprising contacting a compound of Formula 2 with a metal cyanide reagent, a copper(I) salt reagent, an iodide salt reagent and at least one compound of Formula 3 wherein R 1 is NHR 3 or OR 4 ; R 2 is CH 3 or Cl; R 3 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylcyclopropyl, cyclopropylmethyl or methylcyclopropyl; R 4 is H or C 1 -C 4 alkyl; Y is Br or Cl; X is NR 13 or O; n is 0 or 1; and R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 are as defined in the disclosure. Also disclosed is a method for preparing a compound of Formula 2 wherein Y is Br and R 1 is NHR 3 comprising introducing a gas containing bromine into a liquid containing a compound of Formula 4, and further disclosed is a method for preparing a compound of Formula 5 wherein R 14 , R 15 , R 16 and Z are as defined in the disclosure using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above.
1. A method for preparing a compound of Formula 2
wherein
Y is Br;
R 1 is NHR 3;
R 2 is CH 3 or Cl; and
R 3 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylcyclopropyl, cyclopropylmethyl or methylcyclopropyl;
comprising introducing (a) a gas containing bromine into (b) a liquid containing a compound of Formula 4
2. The method of claim 1 wherein R 3 is CH 3 .
3. A method for preparing a compound of Formula 1
wherein
R 1 is NHR 3 ;
R 2 is CH 3 or Cl; and
R 3 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylcyclopropyl, cyclopropylmethyl or methylcyclopropyl;
comprising (A) preparing a compound of Formula 2
wherein Y is Br;
by introducing (a) a gas containing bromine into (b) a liquid containing a compound of Formula 4;
and (B) contacting (1) the compound of Formula 2 with (2) a metal cyanide reagent, (3) a copper(I) salt reagent, (4) an iodide salt reagent and (5) at least one compound of Formula 3
wherein
X is NR 13 or O;
R 5 , R 7 , R 8 , R 9 , R 11 and R 12 are independently H or C 1 -C 4 alkyl;
R 6 and R 10 are independently H, C 1 -C 4 alkyl or phenyl;
R 13 is H or methyl; and
n is 0 or 1;
provided that:
(i) when n is 0, X is NR 13 , and R 5 , R 12 and R 13 are H, then at least two of R 6 , R 7 , R 10 and R 11 are other than H;
(ii) when n is 1, X is NR 13 , and R 5 , R 12 , and R 13 are H, then at least two of R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are other than H;
(iii) when n is 0, X is O, and R 5 and R 12 are H, then at least two of R 6 , R 7 , R 10 and R 11 are other than H;
(iv) when n is 1, X is O, and R 5 and R 12 are H, then at least two of R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are other than H; and
(v) when R 2 is Cl, then Y is Br.