Toluene → HCID 18456485, compound

To a solution of 3-fluoro-4-methoxyacetophenone (2.59 g, 15.4 mmol) and dimethyl oxalate (2.0 g, 16.9 mmol) in THF (25 ml) was portionwise added a 1.7 M solution of potassium tert-amylate in toluene (25 ml, 42.5 mmol). The mixture was stirred at room temperature for 14 hours. Water (1.0 ml) and more THF (25 ml) were added, and stirring at room temperature was continued for 30 hours. Water (250 ml) was added, and the mixture was washed with a mixture of heptane and toluene. The aqueous phase was filtered, acidified with concentrated hydrochloric acid (6.0 ml), and filtered. After drying, 3.09 g (84%) of 4-(3-fluoro-4-methoxyphenyl)-4,2-dioxobutyric acid was obtained. A mixture of this acid (1.99 g, 8.29 mmol), ethanol (75 ml), and hydrazine hydrate (0.80 ml, 2 equiv.) was refluxed for 18 hours. Water (250 ml) and concentrated hydrochloric acid (4.0 ml) were added, and the mixture was filtered. After drying under reduced pressure 1.76 g (90%) of 5-(3-fluoro-4-methoxyphenyl)-2H-pyrazole-3-carboxylic acid acid was obtained as a solid. This acid was used to prepare the title amide using General Procedure (D).

1. stirringstirring at room temperature
2. waitwas continued for 30 hours
3. washthe mixture was washed with a mixture of heptane and toluene
4. filtrationThe aqueous phase was filtered
5. filtrationfiltered
6. customAfter drying

ORD record

ord-6fd29ccd9bd8442497068edda0ed5609

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07208497B2