Potassium Iodide → N-((2S)-5-{[(6-methyl-3-pyridinyl)methyl]oxy}-2,3-dihydro-1H-inden-2-yl)-2-propanesulfonamide

Participants

Reaction Steps

In a 250 ml round-bottomed flask at room temperature under nitrogen, N-[(2S)-5-hydroxy-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (5.31 g, 20.80 mmol, Description 3) was dissolved in N,N-dimethylformamide (25 ml) to give a colourless solution. Cesium carbonate (10.16 g, 31.2 mmol) was then added, followed by 5-(chloromethyl)-2-methylpyridine (4.26 g, 30.1 mmol, Description 6) dissolved in dry N,N-dimethylformamide (20 ml), and potassium iodide (0.863 g, 5.20 mmol). This resulting brown mixture was then allowed to stir at room temperature for the weekend. The mixture was brought to 0° C. and was diluted with water (100 ml) and DCM (150 ml) (exothermic reaction). Phases were separated and the aqueous phase was back extracted with DCM (2×100 ml). The combined organic phases were dried over Na2SO4, filtered and concentrated to give an oily residue, which was diluted in Et2O (250 ml) and washed with water (2×100 ml). The organic was dried again over Na2SO4, filtered and concentrated to give 8.8 g as a brown foam, which was purified by flash-chromatography (100 g SiO2 cartridge, eluting with cyclohexane/EtOAc=60/40, 1/1 and 40/60) to give N-((2S)-5-{[(6-methyl-3-pyridinyl)methyl]oxy}-2,3-dihydro-1H-inden-2-yl)-2-propanesulfonamide (free base) as a pale-yellow solid (3.43 g).

Provenance & Evidence