Methyl 3-mercaptopropionate → Methyl 3-{[5,6-bis(methoxymethoxy)pyridin-3-yl]sulfanyl}propanoate

Participants

Reaction Steps

A solution of 5-bromo-2,3-bis(methoxymethoxy)pyridine (Intermediate 41; 2 g, 7.19 mmol) in dioxane 40.0 ml) was degassed and to this was added DIPEA (2.51 ml, 14.38 mmol), Xantphos (0.333 g, 0.575 mmol) and Pd2(dba)3 (0.263 g, 0.288 mmol). Methyl 3-mercaptopropanoate (0.951 g, 7.91 mmol) was then added as a solution in dioxane (4 mL) and the reaction was heated under reflux for 1 hour before being cooled to room temperature and filtered through a pad of celite, washing with ethyl acetate. The combined organics were washed with water and then brine, dried (MgSO4) and then concentrated in vacuo. The crude product was purified by column chromatography (SiO2; 0-50% ethyl acetate/petrol) to yield methyl 3-{[5,6-bis(methoxymethoxy)pyridin-3-yl]sulfanyl}propanoate (1.65 g, 72%).

Provenance & Evidence