4-Toluenesulfonyl chloride → Methyl 6-(chloromethyl)nicotinate

Participants

Reaction Steps

Methyl 6-methylnicotinate 1-oxide (from Step 1) (6.0 g, 35.9 mmol) was added into the p-toluenesulfonyl chloride (10 g, 52.4 mmol) in 100 mL of 1,4-dioxane. The mixture was heated to reflux for 20 hours. Saturated sodium bicarbonate solution (200 ml) was added into the reaction and the mixture was transferred to separatory funnel. The compound was extracted using ethyl acetate (300 ml×2) and the combined ethyl acetate solution was dried over magnesium sulfate and evaporated to black solid (5.2 g, 78%). LC/MS, tr=1.52 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 186 (M+H). ES-HRMS m/z 186.0314 (M+H calcd for C8H9ClNO2 requires 186.0316).

Provenance & Evidence