Methyl 3-mercaptopropionate → Methyl 3-((5-(methoxymethoxy)-1-(methoxymethyl)-6-oxo-1,6-dihydropyridin-3-yl)thio)propanoate

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Reaction Steps

A mixture of 5-bromo-3-(methoxymethoxy)-1-(methoxymethyl)pyridin-2(1H)-one (Intermediate 15) (3.5 g, 12.6 mmol), Pd2(dba)3 (0.46 g, 0.50 mmol), Xantphos (0.58 g, 1.00 mmol) and DIPEA (4.40 ml, 25.2 mmol) in dioxane (60 ml) was degassed and then placed under an atmosphere of nitrogen. To this mixture was added methyl 3-mercaptopropanoate (1.66 g, 13.8 mmol) and the whole was heated under reflux for 3 hours. Upon cooling it was filtered through a pad of celite and ethyl acetate was washed through the pad of celite to recover any remaining compound. The organic filtrate was washed with water and then saturated aqueous sodium chloride solution and the organics were dried (MgSO4), filtered and concentrated under vacuum. The crude residue was purified by column chromatography (SiO2; 0-100% dichloromethane in petrol, then 0-10% methanol in dichloromethane). Product fractions were collected and concentrated in vacuo to give a yellow oil. This oil was purified further by reverse phase column chromatography (SiO2—C18; 5-95% methanol in water with 0.1% formic acid) to give methyl 3-{[5-(methoxymethoxy)-1-(methoxymethyl)-6-oxo-1,6-dihydropyridin-3-yl]sulfanyl}propanoate (3.4 g, 10.7 mmol, 85%).

Provenance & Evidence