(R)-N-[1-[(3-chlorothien-2-yl)methyl]propyl]-4-methylbenzenesulfonamide → N-(2-fluoro-3-nitropyrid-4-yl)-4-methylbenzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

A first solution containing 43.55 g (0.127 mol) of (R)-N-[1-[(3-chlorothien-2-yl)methyl]propyl]-4-methylbenzenesulfonamide in 71 ml of tetrahydrofuran (THF) is prepared and cooled to 4° C. 138 ml (0.138 mol) of a 1.0 M solution of potassium tert-butoxide in tetrahydrofuran is added dropwise to the first solution. The resulting mixture is stirred for 15 minutes at 20° C. 23.7 g (0.149 mol) of 2,4-difluoro-3-nitropyridine in 10 ml of tetrahydrofuran is then added and the mixture heated at 65° C. for 1 hour. The mixture is cooled to room temperature and partitioned between 150 ml of water and 300 ml of ethyl acetate. The layers are separated. The organic layer is washed twice with 150 ml of water, once with 100 ml of brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is slurried with 100 ml of methanol, then with 150 ml of heptane and then with 60 ml of methanol. The residue is vacuum dried at room temperature with a nitrogen bleed to afford (R)-N-[1-[3-chlorothien-2-yl)methyl]propyl]-N-(2-fluoro-3-nitropyrid-4-yl)-4-methylbenzenesulfonamide (51.1 g, 83.4% yield. 97.6 A% (HPLC)) as a white solid. MS (ion spray)(relative intensity) 484/486 (75), 312 (100).

Provenance & Evidence