Phosphorus oxychloride → 2,6-Bis(trifluoromethyl)-3-methoxycarbonyl-4-chloropyridine

Participants

Reaction Steps

The enamine 2 so produced is then reacted with 2-2.5 equivalents of a strong base, suitably lithium diisopropylamide to generate in situ a dianion which is then reacted with an ester of trifluoromethyl carboxylic acid. The reaction product is a mixture of a substituted 4-hydroxy-2,6-bis-(trifluoromethyl)-3-(methoxycarbonyl)pyridine and a substituted 2,3-dihydro-2-hydroxy-4-pyridone, which dehydrates readily when heated to form a 4-hydroxy-2,6-bis-(trifluoromethyl)-3-(methoxycarbonyl)pyridine 3. The pyridine 3 is then chlorinated with a suitable chlorinating agent such as POCl3 to form 2,6-bis(trifluoromethyl)-3-methoxycarbonyl-4-chloropyridine 4. Pyridine 4 is then hydrogenated using standard laboratory techniques to form 2,6-bis(trifluoromethyl)-3-methoxycarbonyl pyridine 5. The pyridine 5 is then hydrolyzed with a strong base to form 2,6-bis(trifluoromethyl)-3-hydroxycarbonyl pyridine 6. ##STR5##

Provenance & Evidence