Process for the preparation on 2-aminomethylpyridine derivatives
View Patent ↗The present invention relates to a novel process for the preparation of 2-amino-methylpyridine derivatives of the formula (I), comprising reacting in a first step 2-substituted pyridine derivatives of the formula (II), with a nitroalkane of the formula (III), in the presence of a base resulting in 2-nitromethylpyridine derivatives of the formula (IV) and hydrogenating these 2-nitromethylpyridine derivatives of the formula (IV) in a second step in the presence of a catalyst and in the presence of an acid, where in the formulae n, X, Y, R 1 , R 2 and A are as defined in the description.
1. A process for the preparation of 2-aminomethylpyridine derivatives of formula (I) or salts thereof
comprising the steps of reacting 2-substituted pyridine derivatives of the formula (II)
with a nitroalkane of the formula (III)
in the presence of a base resulting in 2-nitromethylpyridine derivatives of the formula (IV)
and then hydrogenating these 2-nitromethylpyridine derivatives of the formula (IV) in the presence of a catalyst and an acid,
wherein
n represents 0, 1, 2 or 3,
X represents a halogen atom,
Y is selected from the group consisting of a halogen atom, halogenoalkyl, alkoxycarbonyl, and alkylsulfonyl, where each Y may be identical or different if n represents, 2 or 3,
R 1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, and cycloalkylmethyl,
R 2 is selected from the group consisting of hydrogen and alkyl, or
R 1 and R 2 taken together can represent alkylene, and
A is selected from the group consisting of halogen, trifluoromethylsulfonyl methylsulphonyl, and other radicals that can act as negatively charged leaving groups.
2. The process of claim 1 , where the base is selected from the group consisting of sodium methanolate, sodium ethanolate, potassium tert-butanolate, sodium tert-butanolate, sodium iso-butanolate, sodium hydroxide, and potassium hydroxide.
3. The process of claim 1 wherein the catalyst is selected from the group consisting of Raney nickel, Raney cobalt, and palladium on carbon.
4. The process of claim 1 wherein the acid is selected from the group consisting of hydrochloric, sulphuric, phosphoric, formic, acetic, propionic, trifluoroacetic, trichloroacetic, and methanesulphonic acids.
5. The process of claim 1 wherein the 2-aminomethylpyridine derivative of formula (I) is 3-chloro-2-nitromethyl-5-trifluoromethylpyridine, the 2-substituted pyridine derivative of the formula (II) is 2,3-dichloro-5-trifluoromethylpyridine, the nitroalkane of the formula (III) is nitromethane, and the 2-nitromethylpyridine derivative of the formula (IV) is 3-chloro-2-nitromethyl-5-trifluoromethylpyridine.
6. The process of claim 5 wherein the base is selected from the group consisting of potassium tert-butanolate and potassium hydroxide.
7. The process of claim 5 wherein the acid is hydrogen chloride.
8. The process of claim 6 wherein the acid is hydrogen chloride.
9. The process of claim 5 wherein the catalyst is palladium on carbon.
10. The process of claim 6 wherein the catalyst is palladium on carbon.
11. The process of claim 7 wherein the catalyst is palladium on carbon.
12. The process of claim 8 wherein the catalyst is palladium on carbon.