HCID 178418361, compound → HCID 178428605, compound

A suspension of 10% palladium on carbon (0.045 g) and 2-hydroxy-4-methyl-3-nitropyridine (0.600 g, 3.89 mmol, 1 equiv) in EtOH (20 mL) was subjected to one atmosphere of hydrogen for 16 hours. After purging the reaction vessel with argon, the mixture was filtered through Whatman #3 paper and the filtrate was evaporated to give 2-hydroxy-4-methyl-3-aminopyridine which was used without further purification. This crude material was stirred in THF (18 mL) at 23° C. Benzyl chloroformate (0.611 mL, 4.28 mmol, 1.1 equiv) and Na2CO3 (0.907 g, 8.56 mmol, 2.2 equiv) were added and the reaction mixture was stirred for 60 h, but TLC showed the reaction to be only 25% complete. The reaction mixture was heated to reflux for 24 h. More benzyl chloroformate (0.611 mL, 4.28 mmol, 1.1 equiv) and Na2CO3 (0.454 g, 4.28 mmol, 1.1 equiv) were added. The reaction mixture was heated to reflux for 24 h more, allowed to cool, diluted with EtOAc (200 mL), washed with half-saturated brine (2×40 mL), dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography (gradient elution, 3→5% CH3OH in CH2Cl2) to provide the title intermediate (0.363 g, 35%) as a white solid: 1H NMR (DMSO-d6) δ 2.02 (s, 3H), 3.31-3.35 (m, 2H), 5.06 (s, 2H), 6.83 (d, 1H, J=6.7), 7.17 (d, 1H, J=6.7), 7.28-7.39 (m, 5H); Anal. C14H14N2O3: C, H, N.

1. customAfter purging the reaction vessel with argon
2. filtrationthe mixture was filtered through Whatman #3 paper
3. customthe filtrate was evaporated

ORD record

ord-ec34c12e956d42239ec0f105bfe2a9e0

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06514997B2