Formaldehyde → 2-(2-Methoxy-5-(4-methoxyphenyl)pyridin-4-yl)ethanol

Participants

Reaction Conditions

Reaction Steps

According to Scheme 30 Step 2: To a stirred solution of 2-methoxy-5-(4-methoxyphenyl)-4-methylpyridine (1 eq, 10.0 mmol, 2.30 g) in anhydrous THF (66 mL) at −78° C. under argon was added dropwise butyl lithium (2.5M, 1.5 eq, 15.1 mmol, 6.0 mL). The reaction mixture was stirred for one hour and then allowed to warm slowly to 0° C. and stirred at 0° C. for a further 30 minutes. The reaction mixture was then cooled to −78° C. and paraformaldehyde (6.07 g) was added. The reaction mixture was then allowed to warm to room temperature and was stirred for 2 hours. The reaction was quenched with saturated aqueous NH4Cl (30 mL), diluted with AcOEt and the aqueous phase was extracted (×3). The combined organic fractions were dried (Na2SO4), filtered and concentrated under reduced pressure. HCl 3M (15 mL) was added to the solution of the crude residue diluted in acetonitrile (10 mL). The reaction mixture was stirred for 2 hours at 60° C. The aqueous phase was extracted with Et2O, then neutralized with NaHCO3 (40 mL). The aqueous phase was extracted with CH2Cl2. The combined organic fractions were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel (AIT Flashsmart prepacked column 20 g SiO2) using CH2Cl2/AcOEt (99/1) as the eluent to afford 2-(2-methoxy-5-(4-methoxyphenyl)pyridin-4-yl)ethanol (0.62 mmol, 0.16 g, 6%) as a colorless oil.

Provenance & Evidence