Potassium Carbonate → 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acid

Temperature

80 °C

To a solution of methyl 4-bromo-5-methyl-2-furancarboxylate (500 mg, 2.28 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (950 mg, 4.57 mmol) [prepared according to Preparation 7] and potassium carbonate (315 mg, 2.28 mmol) in 1,4-dioxane (8 mL) and water (2.0 mL) was added bis(tri-t-butylphosphine)Palladium (0) (117 mg, 0.23 mmol). The mixture was heated to 80° C. and after 15 h the reaction mixture was concentrated. The residue was partitioned between DCM and water. The organic layer was concentrated and dissolved in tetrahydrofuran (THF) (8.0 mL). The solution was treated with 6N aqueous solution of sodium hydroxide (3.80 mL, 22.83 mmol) and heated to 75° C. After 15 h, the reaction mixture was concentrated and partitioned between DCM and water. The aqueous layer was acidified to pH ˜3 with 2N HCl aqueous solution and extracted several times with DCM. The organic fractions were combined and concentrated to afford the title compound as a yellow solid (401 mg, 1.95 mmol, 85% yield): LC-MS (ES) m/z 207 (M+H)+.

1. concentrationwas concentrated
2. customThe residue was partitioned between DCM and water
3. concentrationThe organic layer was concentrated
4. dissolutiondissolved in tetrahydrofuran (THF) (8.0 mL)
5. temperatureheated to 75° C
6. concentrationthe reaction mixture was concentrated
7. custompartitioned between DCM and water
8. extractionextracted several times with DCM
9. concentrationconcentrated

ORD record

ord-6370e9c888614d5abb949aac2e695d40

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946278B2