Patent ID: 7498439

Claim:
A process for the preparation of a heteroaryl acetamide from a heteroaryl α-hydroxyacetamide, the process comprising directly hydrogenating a heteroaryl α-hydroxyacetamide in the presence of hydrogen gas in a reaction mixture comprising a solvent system, the heteroaryl α-hydroxyacetamide, at least one strong acid, a halide and a precious metal catalyst, wherein the reaction mixture has a molar ratio of the starting heteroaryl α-hydroxyacetamide to water at the initiation of hydrogenolysis of at least about 2:1, the heteroaryl α-hydroxyacetamide corresponding to Formula 1 and the heteroaryl acetamide product corresponding to Formula 1A: wherein Z is O, NR 20 or CR 21 ; X 1 and X 2 are independently selected from the group consisting of hydrogen, halogen, C 1-4 alkoxy, C 1-6 alkyl, —CF 3 and CH 3 SO 2 —; R 1 and R 2 are independently hydrogen or hydrocarbyl; R 10 is hydrogen, halogen, C 1-4 alkyl, or a member of a fused ring wherein the fused ring is (i) a substituted or unsubstituted, saturated or unsaturated, five or six-membered, heterocyclic or carbocyclic ring fused to the A ring comprising R 10 , the carbon atom to which R 10 is attached, R 20 , and the nitrogen atom to which R 20 is attached, or (ii) a six-membered, aromatic, carbocyclic ring fused to the A ring comprising R 10 , R 11 , and the carbon atoms to which R 10 and R 11 are attached, optionally substituted with Y at a substitutable position thereof; R 11 is hydrogen, halogen, C 1-4 alkyl, or a member of a fused ring wherein the fused ring is (i) a six-membered, aromatic, carbocyclic ring fused to the A ring comprising R 10 , R 11 , and the carbon atoms to which R 10 and R 11 are attached, optionally substituted with Y at a substitutable position thereof, or (ii) a six-membered, aromatic, carbocyclic ring fused to the A ring comprising R 11 , R 12 , and the carbon atoms to which R 11 and R 12 are attached, optionally substituted with Y at a substitutable position thereof; R 12 , if present, is hydrogen, halogen, C 1-4 alkyl, or a member of a fused ring wherein the fused ring is (i) a six-membered, aromatic, carbocyclic ring fused to the A ring comprising R 11 , R 12 , and the carbon atoms to which R 11 and R 12 are attached, optionally substituted with Y at a substitutable position thereof; R 20 is C 1-5 alkyl or a member of a fused ring wherein the fused ring is a substituted or unsubstituted, saturated or unsaturated, five or six-membered, heterocyclic or carbocyclic ring fused to the A ring comprising R 10 , the carbon atom to which R 10 is attached, R 20 , and the nitrogen atom to which R 20 is attached; R 21 is hydrogen, halogen or C 1-4 alkyl; n is 0 or 1; each Y is independently hydrogen, halogen or C 1-4 alkyl; and when Z is CR 21 , the A ring is aromatic.