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

HRID 1253120Notes

Reaction equation

HRID 1253120 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7](O)[CH:6]=[C:5]([C:14]([F:17])([F:16])[F:15])[N:4]=1.O=P(Cl)(Cl)[Cl:22]>>[F:1][C:2]([F:19])([F:18])[C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([Cl:22])[CH:6]=[C:5]([C:14]([F:17])([F:16])[F:15])[N:4]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178498966Methyl 2,6-bis(trifluoromethyl)-4-hydroxy-3-pyridinecarboxylate

Product 1

HCID 138828782,6-Bis(trifluoromethyl)-3-methoxycarbonyl-4-chloropyridine

Procedure

The Route A below schematically depicts a method whereby the substituted pyridine compounds of this invention may be prepared from compounds which are known in the art. In this route, acetone dicarboxylic acid 1 is cyclized into the corresponding anhydride 2 by reacting it with acetic anhydride. The anhydride 2 is dissolved in methanol and stirred to form the acetone dicarboxylic acid monomethyl ester 3. The monomethyl ester is then reacted with isobutylene in acid and a suitable organic solvent to form t-butyl, methyl acetone dicarboxylate 4. The dicarboxylate 4 is then sequentially reacted with magnesium chloride in a suitable organic solvent and with trifluoroacetic anhydride to form methyl, t-butyl diesterpyrone 5.The pyrone 5 is then reacted with trifluoroacetic acid to form the acid methyl ester pyrone 6. The pyrone 6 is then refluxed in a suitable organic solvent to remove the acid moiety and form the methyl ester pyrone 7. The pyrone 7 is then aminated by addition of methanol and ammonia to form 2,6-bis(trifluoromethyl)-3-methoxycarbonyl-4-hydroxy pyridine 8. Pyridine 8 is then chlorinated with a suitable chlorinating agent such as POCl3 to form 2,6-bis(trifluoromethyl)-3-methoxycarbonyl-4-chloropyridine 9. Pyridine 9 is then hydrogenated using standard laboratory techniques to form 2,6-bis(trifluoromethyl)-3-methoxycarbonyl pyridine 10. The pyridine 10 is then hydrolyzed with a strong base to form 2,6-bis(trifluoromethyl)-3-hydroxycarbonyl pyridine 11. ##STR4##

Sources & evidence

ORD record
ord-73482df5086f483f9c101768f516a5f6
Source dataset
uspto-grants-1988_05
Patent number
US04747871

Reaction notes

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