Object of the present invention is an efficient process for the preparation of the active pharmaceutical ingredient Sitagliptine and the 2,4,5-trifluorophenylacetic acid (TFAA) and salt thereof, which is a key intermediate for the synthesis of Sitagliptine.

##STR00001##

The invention belongs to the pharmaceutical manufacturing field, which relates to a novel process for the preparation of substituted phenylacetic acids derivatives, especially relates to the preparation of 2-(4-(2-oxocyclopentyl)phenyl)propanoic acid. The process for the preparation of the precursor form of loxoprofen which use 1,4-di-halobenzyl compounds or disubstituted benzyl compounds as starting material, is through the substitution reaction of cyclopentanone groups or its precursor compounds.

##STR00001##

Wherein X is halogen, L.sub.1 is a suitable leaving group selected from halogen, OH, OMs, OTs, OTf and the like; L.sub.2 is a suitable leaving group selected from halogen, CN, OH, CH.sub.2OH, CHO, CH.sub.3NO.sub.2, ester group, NR.sub.4R.sub.5, OTf, OTs, OMs, CCR.sub.6, CCR.sub.7 and the like, wherein R.sub.4, R.sub.5, R.sub.6, R.sub.7 are short chain alkyl groups; Z is cyclopentanone group and its precursor form selected from

##STR00002##

and the like; R.sub.3 is short chain alkyl groups. L.sub.3 is a suitable leaving group selected from halogen, OH, OMs, OTs, OT.sub.f and the like, or organometallic groups. The invention also include the detailed procedure to convert the precursor compounds of cyclopentanone group to cyclopentanone, followed by the transformation of the precursor compounds of loxoprofen to loxoprofen.

The invention belongs to the pharmaceutical manufacturing field, which relates to a novel process for the preparation of substituted phenylacetic acids derivatives, especially relates to the preparation of 2-(4-(2-oxocyclopentyl)phenyl)propanoic acid. The process for the preparation of the precursor form of loxoprofen which use 1,4-di-halobenzyl compounds or disubstituted benzyl compounds as starting material, is through the substitution reaction of cyclopentanone groups or its precursor compounds.

##STR00001##

Wherein X is halogen, L.sub.1 is a suitable leaving group selected from halogen, OH, OMs, OTs, OTf and the like; L.sub.2 is a suitable leaving group selected from halogen, CN, OH, CH.sub.2OH, CHO, CH.sub.3NO.sub.2, ester group, NR.sub.4R.sub.5, OTf, OTs, OMs, CCR.sub.6, CCR.sub.7 and the like, wherein R.sub.4, R.sub.5, R.sub.6, R.sub.7 are short chain alkyl groups; Z is cyclopentanone group and its precursor form selected from

##STR00002##

and the like; R.sub.3 is short chain alkyl groups. L.sub.3 is a suitable leaving group selected from halogen, OH, OMs, OTs, OT.sub.f and the like, or organometallic groups. The invention also include the detailed procedure to convert the precursor compounds of cyclopentanone group to cyclopentanone, followed by the transformation of the precursor compounds of loxoprofen to loxoprofen.

The invention belongs to the pharmaceutical manufacturing field, which relates to a novel process for the preparation of substituted phenylacetic acids derivatives, especially relates to the preparation of 2-(4-(2-oxocyclopentyl)phenyl)propanoic acid. The process for the preparation of the precursor form of loxoprofen which use 1,4-di-halobenzyl compounds or disubstituted benzyl compounds as starting material, is through the substitution reaction of cyclopentanone groups or its precursor compounds.

##STR00001##

Wherein X is halogen, L.sub.1 is a suitable leaving group selected from halogen, OH, OMs, OTs, OTf and the like; L.sub.2 is a suitable leaving group selected from halogen, CN, OH, CH.sub.2OH, CHO, CH.sub.3NO.sub.2, ester group, NR.sub.4R.sub.5, OTf, OTs, OMs, CCR.sub.6, CCR.sub.7 and the like, wherein R.sub.4, R.sub.5, R.sub.6, R.sub.7 are short chain alkyl groups; Z is cyclopentanone group and its precursor form selected from

##STR00002##

and the like; R.sub.3 is short chain alkyl groups. L.sub.3 is a suitable leaving group selected from halogen, OH, OMs, OTs, OT.sub.f and the like, or organometallic groups. The invention also include the detailed procedure to convert the precursor compounds of cyclopentanone group to cyclopentanone, followed by the transformation of the precursor compounds of loxoprofen to loxoprofen.

A process for preparing azelaic acid is disclosed. In particular, the process for preparing azelaic acid is an ozone free process. The process for preparing azelaic acid comprises a step of decarboxylation of tetra-carboxylic acid in the presence of a organic sulfonic acid.

A process for preparing azelaic acid is disclosed. In particular, the process for preparing azelaic acid is an ozone free process. The process for preparing azelaic acid comprises a step of decarboxylation of tetra-carboxylic acid in the presence of a organic sulfonic acid.

A long-life catalyst which can be easily and inexpensively manufactured and has high activity and suppressed leakage of metal. A catalyst according to some embodiments includes: a substrate; and a first metal atom as a catalytic center. The substrate contains a non-metallic atom and a second metal atom, and the non-metallic atom is any one selected from the group consisting of a group 15 element, a group 16 element and a group 17 element.

A long-life catalyst which can be easily and inexpensively manufactured and has high activity and suppressed leakage of metal. A catalyst according to some embodiments includes: a substrate; and a first metal atom as a catalytic center. The substrate contains a non-metallic atom and a second metal atom, and the non-metallic atom is any one selected from the group consisting of a group 15 element, a group 16 element and a group 17 element.

A long-life catalyst which can be easily and inexpensively manufactured and has high activity and suppressed leakage of metal. A catalyst according to some embodiments includes: a substrate; and a first metal atom as a catalytic center. The substrate contains a non-metallic atom and a second metal atom, and the non-metallic atom is any one selected from the group consisting of a group 15 element, a group 16 element and a group 17 element.

The present invention refers to a process for a transition metal, particularly nickel-catalyzed cyanation reaction of aryl/vinyl halide using organic nitrile compounds. This new reaction provides a strategically distinct approach to the safe preparation of aryl/vinyl cyanides, which are essential compounds in agrochemistry and medicinal chemistry.