Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid
AssigneeZambon Group S.p.A.
InventorsClaudio Giordano, Laura Coppi, Francesco Minisci
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Abstract
A process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid comprising the reaction of an organometallic derivative with a suitable substituted benzene in the presence of a transition-metal based catalyst is described.
Claims12
A process for the preparation of a biphenyl derivative of formula ##STR6## comprising the reaction between a difluorophenyl organometallic derivative of formula ##STR7## and a phenol compound of formula ##STR8## or the reaction between a phenol organometallic derivative of formula ##STR9## and a difluorophenyl compound of formula ##STR10## wherein Q is a copper atom or an MX.sub.n group where M is a metal selected from the group consisting of Mg, Zn, Cd, Hg, B and Al
- with the proviso when M is Mg, Zn, Cd or Hg, X is Cl, Br or I and n is 1;
- when M is B, X is Cl, Br, I, OH, a C.sub.1-3 alkoxy and n is 2;
- when M is Al, X is C.sub.1-4 alkyl and n is 2;
- Y is selected from the group consisting of Cl, Br, I and a trifluoromethanesulfonyloxy group;
- wherein R is selected from the group consisting of a hydrogen atom, a linear or branched C.sub.1-5 alkyl, phenyl, substituted phenyl and benzyl;
- R.sub.1 is selected from the group consisting of a hydrogen atom, a carboxyl group and a carboxyl precursor group;
- in the presence of a zero valent transition-metal based catalyst.
A process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid comprising:
- i) reacting a difluorophenyl organometallic derivative of formula ##STR11## and a phenyl compound of formula ##STR12## or reacting a phenyl organometallic derivative of formula ##STR13## and a difluorophenyl compound of formula ##STR14## wherein Q is a copper atom or an MX.sub.n group where M is a metal selected from the group consisting of Mg, Zn, Cd, Hg, B and Al
- with the proviso when M is Mg, Zn, Cd or Hg, X is Cl, Br or I and n is 1;
- when M is B, X is Cl, Br, I or OH, a C.sub.1-3 alkoxy and n is 2;
- when M is Al, X is C.sub.1-4 alkyl and n is 2;
- Y is selected from the group consisting of Cl, Br, I or a trifluoromethanesulfonyloxy group;
- wherein R is selected from the group consisting of a hydrogen atom, a linear or branched C.sub.1-5 alkyl, phenyl, substituted phenyl or benzyl;
- R.sub.1 is selected from the group consisting of a hydrogen atom, a carboxyl group and a carboxyl precursor group;
- in the presence of a zero valent transition-metal based catalyst;
- ii) hydrolyzing the --OR ether group when R.sub.1 .noteq.H;
- and
- iii) carboxylating the R.sub.1 group when R.sub.1 =H.
Dependencies are inferred from the claim text.