Sodium Carbonate → 3-Pyridinecarboxylic acid, 1,1-dimethylethyl ester

Temperature

100 °C

tert-butyl-6-bromo-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (19.8 g, 50.0 mmol), bis(pinacolato)diboran (14.0 g, 55.0 mmol), Pd(OAc)2 (560 mg, 2.50 mmol), DPPF (2.77 g, 5.00 mmol), and AcOK (5.82 g, 60.0 mmol) were suspended in dioxane (250 mL) and heated at 100° C. for 10 hours. After cooling down to room temperature, 5-bromo-nicotinic acid tert-butyl ester (14.2 g, 55.0 mmol), Pd(PPh3)4 (5.78 g, 5.00 mmol) and 2M Na2CO3 aq. (125 mL, 250 mmol) were added to the reaction mixture; and then heated at 100° C. for 15 hours. The reaction mixture was diluted with EtOAc and H2O, organic layer was washed with brine and dried over MgSO4. After filtration, the solvents were removed in vacuo and the residue was purified by silica gel column chromatography (hexane/EtOAc=10/0 to 6/4) and the obtained brown solid was crystallized from EtOAc/hexane (1/1) to afford 5-{1′-tert-butoxycarbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid tert-butyl ester as a pale yellow solid.

1. temperatureAfter cooling down to room temperature
2. temperatureand then heated at 100° C. for 15 hours
3. washwas washed with brine
4. dry with materialdried over MgSO4
5. filtrationAfter filtration
6. customthe solvents were removed in vacuo
7. customthe residue was purified by silica gel column chromatography (hexane/EtOAc=10/0 to 6/4)
8. customthe obtained brown solid was crystallized from EtOAc/hexane (1/1)

ORD record

ord-7d3fb9ad22a1491aab38b03b5b47e941

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093389B2