1,4-Difluorobenzene → 4-(2',5'-Difluorobenzoyl)pyridazine-5-carboxylic acid

HRID 234805

Reaktionsgleichung

C([Li])(CC)C.[F:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[N:14]1[CH:19]=[C:18]2[C:20]([O:22][C:23](=[O:24])[C:17]2=[CH:16][N:15]=1)=[O:21].[Cl-].[NH4+]>O1CCCC1>[F:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[C:20]([C:18]1[C:17]([C:23]([OH:24])=[O:22])=[CH:16][N:15]=[N:14][CH:19]=1)=[O:21]

Komponenten

Reaktionsbedingungen

Temperatur: -80 °C

Versuchsvorschrift

Sec-butyllithium (1.32 M in cyclohexane; 1.25 mL) is added dropwise via syringe over 0.25 h to a stirred solution of 1,4-difluorobenzene (0.162 g) in tetrahydrofuran (THF) (5 mL) at -84° C. under a nitrogen atmosphere. The yellow mixture is stirred for an additional 45 min at -80° C. and then added via a canula over 5 min to a stirred solution of pyridazine 4,5-dicarboxylic acid anhydride (0.22 g; prepared according to J.Het Chem. 14, 1099, (1977)) in THF at -80° C. by nitrogen pressure. The mixture is warmed to room temperature overnight and neutralized with amonium chloride. After removal of THF at reduced pressure the resultant tan solid is treated with an aqueous sodium bicarbonate solution (10 mL) and washed with diethyl ether (10 mL). The aqueous phase is acidified with aqueous hydrochloric acid. The precipitate is collected by filtration, washed with cold water (3×10 mL) and dried to give 4-(2',5'-difluorobenzoyl)pyridazine-5-carboxylic acid (0.23 g) as an off-white solid, m.p. 202°-205° C.

Aufarbeitung

customAfter removal of THF at reduced pressure the resultant tan solid
additionis treated with an aqueous sodium bicarbonate solution (10 mL)
washwashed with diethyl ether (10 mL)
filtrationThe precipitate is collected by filtration
washwashed with cold water (3×10 mL)
customdried

Quellen und Nachweise

ORD-Eintrag: ord-0e9afc5dc40845d1a58a356be22fd549
Quelldatensatz: uspto-grants-1997_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US05596097

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