Isoamyl Nitrite → Nicotinic Acid

HRID 487858Notes

Reaction equation

[Na].C([C:5]1[C:6](CC(C)C)=[C:7]([C:18]([O:20]C)=[O:19])[C:8](C(F)F)=[N:9][C:10]=1C(F)(F)F)(=O)C.N(OCCC(C)C)=O>CO>[N:9]1[CH:10]=[CH:5][CH:6]=[C:7]([C:18]([OH:20])=[O:19])[CH:8]=1

Participants

Conditions

Temperature: 25 °C

Procedure

This example illustrates the preparation of Compound 101 an examples of the formation of the heterocycle by cycloaddition reaction. Sodium (7.87 g, 0.35 mol) was cautiously added in portions to 250 mL methanol under nitrogen. Methyl 5-acetyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (20 g, 0.057 mol) was added at 25° C., followed by dropwise addition of isoamyl nitrite (33.15 g, 0.283 mol). The mixture was stirred overnight at 25° C., then quenched with ice/concentrated HCl slush, and extracted with ether. The combined ether layers were washed with saturated sodium bicarbonate and dried (MgSO4). The solvent was evaporated in vacuo and the residue purified by HPLC with 10% ethyl acetate-hexane to give 22 g (99%) of 3-pyridinecarboxylic acid, 2-(difluoromethyl)-5-((hydroxyimino)acetyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester, as a yellow solid. m.p. 84°-86° C.

Workup

customby cycloaddition reaction
customquenched with ice/concentrated HCl slush
extractionextracted with ether
washThe combined ether layers were washed with saturated sodium bicarbonate
dry with materialdried (MgSO4)
customThe solvent was evaporated in vacuo
customthe residue purified by HPLC with 10% ethyl acetate-hexane

Sources & evidence

ORD record: ord-047ac20e6bb042049d62d6e272ed5fee
Source dataset: uspto-grants-1994_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05298479

Reaction notes

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