Methyl 3-methylpyridine-2-carboxylate → (3-Methylpyridin-2-yl)methanol

HRID 2041308Notes

Reaction equation

C[O:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][N:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:2][CH2:3][C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][N:6]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Heat a mixture of 3-methylpicolinic acid (1.0 g, 7.3 mmol), potassium carbonate (4.1 g, 29.7 mmol), and iodomethane (4.4 g, 31.0 mmol) in acetone (35 mL) overnight under reflux. Filter, wash the residue with EtOAc, and concentrate in vacuo. Pass through a short plug of silica gel eluting with hexane/EtOAc (1:1) to provide 2-methoxycarbonyl-3-methylpyridine as a pale yellow liquid (630 mg, 57%). To a solution of 2-methoxycarbonyl-3-methylpyridine in anhydrous THF (10 mL) at 0° C., add with stirring a solution of 1M lithium aluminum hydride in THF (5 mL, 5 mmol), and continue stirring for 30 min at 0° C. Allow the mixture to warm to ambient temperature and quench cautiously with 0.5M aqueous NaOH. Heat the mixture at 60° C. for 40 min, cool to ambient temperature, extract with EtOAc, dry over anhydrous Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (4:3) to give the desired intermediate (90 mg, 18%).

Workup

temperatureAllow the mixture to warm to ambient temperature
customquench cautiously with 0.5M aqueous NaOH
temperatureHeat the mixture at 60° C. for 40 min
temperaturecool to ambient temperature
extractionextract with EtOAc
dry with materialdry over anhydrous Na2SO4
concentrationconcentrate in vacuo
customPurify by chromatography on silica gel eluting with hexane/EtOAc (4:3)

Sources & evidence

ORD record: ord-7f0475bfc5284d44a3b79c1731f91898
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580780B2

Reaction notes

Loading…