Potassium Carbonate → [1-(Tetrahydro-pyran-2-yl)-1H-indazol-4-yl]acetic acid

Temperature

80 °C

A mixture of 4-bromomethyl-1-(tetrahydro-pyran-2-yl)-1H-indazole (2.43 g, 8.232 mmol), dichlorobis(triphenylphosphine)palladium(II) (314 mg, 0.447 mmol), pulverized potassium carbonate (1.3 g, 9.406 mmol), THF (95 mL) and methanol (12 mL) was stirred at 25° C. in a sealed tube under 40 psi of carbon monoxide for 3 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (3×150 mL). The organic layers were combined, washed with brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. To the resulting brown oil was added THF (20 mL), water (12 mL) and lithium hydroxide monohydrate (3.4 g, 81.03 mmol) at 25° C. and heated at 80° C. for 90 min. The reaction mixture was cooled, diluted with water (100 mL) and washed with ether (2×50 mL). The aqueous layer was acidified with aqueous 6N HCl, saturated with sodium chloride and extracted with ethyl acetate (3×150 mL). The organic layers were combined, washed with brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give [1-(Tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetic acid (1.85 g, 86.3%) as a yellow gum which solidified. MS m/e 261.3 (M+H+).

1. extractionextracted with ethyl acetate (3×150 mL)
2. washwashed with brine (100 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. temperatureThe reaction mixture was cooled
7. washwashed with ether (2×50 mL)
8. extractionextracted with ethyl acetate (3×150 mL)
9. washwashed with brine (100 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure

ORD record

ord-b5b942f9c01b4d1588454a8ba231aa58

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404859B2