Reaktion #217671

Reaktionsgleichung

5-methoxyanthranilic acid

sodium nitrite

hydrazine

3-hydroxy-1-(4-iodo-phenyl)-4-(2,2,2-trifluoro-acetyl)-5,6-dihydro-1H-pyridin-2-one

acetic acid

→

2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid methyl ester

Ausbeute 24.0%

Lösungsmittel

hydrochloric acid

water

hydrochloric acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe precipitate was agitated
2. 2
   workup.WAITkept at 0° C. for 30 minutes
3. 3
   Filtrationfiltered
4. 4
   WaschenThe solids were washed successively with ice cold brine and petroleum ether
5. 5
   Sonstigedried under a stream of air
6. 6
   Temperaturheated to 80° C
7. 7
   SonstigeUpon completion of the reaction the solvent
8. 8
   Sonstigewas evaporated to a viscous oil which

Vorschrift

Part A: To a 0° C. solution of 5-methoxyanthranilic acid (5.0 g, 29.9 mmol) in concentrated hydrochloric acid (10 mL) was added dropwise an ice cold solution of sodium nitrite (2.06 g, 29.9 mmol) in water (5 mL) and stirring was continued at 0° C. for 30 minutes. Stannous chloride dihydrate (16.8 g, 74.8 mmol) was dissolved in concentrated hydrochloric acid (16 mL), cooled to 0° C., and added slowly to the solution of the diazonium salt. The precipitate was agitated, kept at 0° C. for 30 minutes, and then filtered. The solids were washed successively with ice cold brine and petroleum ether and dried under a stream of air and then under vacuum. The crude hydrazine salt and 3-hydroxy-1-(4-iodo-phenyl)-4-(2,2,2-trifluoro-acetyl)-5,6-dihydro-1H-pyridin-2-one (12.3 g, 29.9 mmol) were combined in glacial acetic acid (50 mL) and heated to 80° C. Upon completion of the reaction the solvent was evaporated to a viscous oil which was subjected to silica gel column chromatography to yield 2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid methyl ester (4.12 g, 24%). MS (AP+) 571.9 (100%).

Quelle