Water → HCID 66602080, compound

Participants

Reaction Steps

To a solution of t-butyl 4-(aminomethyl)tetrahydropyridine-1(2H)-carboxylate (1.50 g, 7.0 mmol, 1 eq) in DCM (anhydrous) (20 mL) is added methanesulfonyl chloride (569 μL, 7.35 mmol, 1.05 eq). To this add triethylamine (2.05 ml, 14.7 mmol, 2.1 eq), dropwise over 15 min. Stir at room temperature for 3 hr. and then add water (20 mL) with stirring. The organic phase is isolated then washed with 2 M aqueous hydrochloric acid (20 mL), and saturated aqueous sodium hydrogen carbonate solution (20 mL). Dry the organic layer (magnesium sulphate) and concentrate to give 4-(methanesulfonyl-aminomethyl)-piperidine-1-carboxylic acid t-butyl ester (2.1 g, 102%). MS (ES): m/z=315.1 [M+Na]+. To a solution of this compound (2.1 g, 7.2 mmol, 1 eq) in 1,4-dioxane (25 mL) add 4 M hydrogen chloride in dioxane (17.95 mL, 72 mmol, 10 eq). Stir at room temperature for 29 hr., basify with 2 M aqueous sodium hydroxide, and then add DCM (20 mL). Separate the layers and extract the aqueous twice with DCM (20 mL), dry the combined organics over magnesium sulphate, filter and concentrate. Extract the aqueous layer a further four times with 3:1 chloroform:isopropanol (25 mL). Concentrate the aqueous layer to less than 10 mL volume and extract again with four times with 3:1 chloroform:isopropanol (25 mL). Combine with all the previous organic extracts to give N-piperidin-4-ylmethyl-methanesulfonamide (703 mg, 50%). MS (m/z): 193 (M+1).

Provenance & Evidence