Process for preparing 4-(2,4-difluorophenyl)-salicyclic acid
AssigneeMerck & Co., Inc.
InventorsHoward Jones, Robert W. Houser
Life of this patent
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Abstract
5-(2,4-difluorophenyl)salicylic acid, an anti-inflammatory, anti-pyretic, analgesic agent is prepared by: (1) diazotizing 2,4-difluoroaniline in the presence of benzene to yield 2,4-difluorobiphenyl; (2) Friedel-Crafts acylation to produce 2',4'-difluoro-4-alkanoylbiphenyl; (3) oxidation of the alkanoyl group to produce 2',4'-difluoro-4-alkanoyloxybiphenyl; (4) hydrolysis of the alkanoyl group to produce 4-(2,4-difluorophenyl)phenol; and (5) Kolbe-Schmitt carboxylation to produce the final product.
Claims8
A process for the preparation of a compound of formula:
- ##STR7## which comprises in sequence, the following steps:
- (a) diazotizing 2,4-difluoroaniline in the presence of benzene to produce 2,4-difluorobiphenyl;
- (b) acylating the product of Step (a) in the presence of a Friedel-Crafts catalyst with a C.sub.2-5 alkanoic acid anhydride or C.sub.2-5 alkanoic acid halide to produce 4-(C.sub.2-5 alkanoyl)-2',4'-difluorobiphenyl;
- (c) oxidizing the C.sub.2-5 alkanoyl group of the product of Step (b) to produce 4-(C.sub.2-5 alkanoyloxy)-2',4'-difluorobiphenyl;
- (d) hydrolyzing the C.sub.2-5 alkanoyl group from the product of Step (c) to produce 4-(2,4-difluorophenyl)phenol or alkali metal salt thereof;
- (e) carboxylating the product of Step (d) to produce the product 5-(2,4-difluorophenyl)salicylic acid.
A process for the preparation of a compound of formula:
- ##STR8## which comprises in sequence the steps of:
- (a) acylating 2,4-difluorobiphenyl with a C.sub.2-5 alkanoic acid anhydride or C.sub.2-5 alkanoic acid halide in the presence of a Friedel-Crafts catalyst to produce 4-(C.sub.2-5 alkanoyl)-2',4'-difluorobiphenyl;
- (b) oxidizing the product of Step (a) to produce 4-(C.sub.2-5 alkanoyloxy)-2',4'-difluorobiphenyl;
- (c) hydrolyzing the C.sub.2-5 alkanoyl group from the product of Step (b) to produce 4-(2,4-difluorophenyl)phenol or alkali metal salt thereof;
- (d) carboxylating the product of Step (c).
A process for the preparation of a compound of formula:
- ##STR9## which comprises in sequence the steps of:
- (a) oxidizing a compound of formula:
- ##STR10## to produce the compound of formula:
- ##STR11## (b) hydrolyzing the product of Step (a) to produce 4-(2,4-difluorophenyl)phenol or alkali metal salt thereof;
- (c) carboxylating the product of Step (b).
A process for the preparation of a compound of formula:
- ##STR12## which comprises in sequence the steps of:
- (a) hydrolyzing a compound of formula:
- ##STR13## to produce 4-(2,4-difluorophenyl)phenol or alkali metal salt thereof;
- and (b) carboxylating the product of Step (a).
Dependencies are inferred from the claim text.