Method and intermediates for the preparation of 2,2,2-trifluoro-N-(4-fluoro-3-pyridin-4-yl-benzyl)-acetamide hydrochloride
The present invention is directed to a method for the preparation of 2,2,2-trifluoro-n-(4-fluoro-3-pyridin-4-yl-benzyl)-acetamide hydrochloride of the formula: and reaction intermediates used in the method.
1. A compound selected from the group consisting of:
4-fluoro-3-pyridin-4-yl-benzylamine
and
2,2,2-trifluoro-N-(4-fluoro-3-pyridin-4-yl-benzyl)-acetamide hydrochloride
2. A method for preparing 2,2,2-trifluoro-N-(4-fluoro-3-pyridin-4-yl-benzyl)-acetamide hydrochloride according to claim 1 comprising
A) coupling 3-bromo-4-fluorobenzylamine hydrochloride and pyridine-4-boronic acid under Suzuki coupling conditions to yield 4-fluoro-3-pyridin-4-yl-benzylamine, and
B) converting the 4-fluoro-3-pyridin-4-yl-benzylamine to 2,2,2-trifluoro-N-(4-fluoro-3-pyridin-4-yl-benzyl)-acetamide hydrochloride by trifluoroacetylation using a trifluoroacetylating agent under trifluoroacetylating conditions.
3. The method according to claim 2 wherein the Suzuki coupling conditions uses a Suzuki coupling solvent selected from
a) an alcoholic solvent with a boiling point of at least that of i-propyl alcohol,
b) polar aprotic solvent,
c) ethereal solvent, or
d) mixture of any of the aforesaid solvents;
and water or toluene.
4. The method according to claim 3 wherein the Suzuki coupling solvent comprises an alcoholic solvent with a boiling point of at least that of i-propyl alcohol.