Phosphorus oxychloride → 2,6-Bis(trifluoromethyl)-3-methoxycarbonyl-4-chloropyridine
Reaction equation
O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[C:3]=1[C:16]([O:18][CH3:19])=[O:17].O=P(Cl)(Cl)[Cl:22]>>[F:13][C:12]([F:15])([F:14])[C:4]1[C:3]([C:16]([O:18][CH3:19])=[O:17])=[C:2]([Cl:22])[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=1Participants
Procedure
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##
Sources & evidence
- ORD record
- ord-90ffd26c91244da4970e9989ffcbcbe3
- Source dataset
- uspto-grants-1988_05
- Patent number
- US04747871
Reaction notes
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