1-BENZENESULFONYL-PIPERIDINE-3-CARBOXYLIC ACID synthesis

Yield:321970-54-1 97.83%

Reaction Conditions:

Stage #1: nipecotic acidwith sodium carbonate in water at 0; for 0.166667 h;
Stage #2: benzenesulfonyl chloride in water at 0 - 20;
Stage #3: with hydrogenchloride in water at 0 - 5; pH=3; for 0.25 - 0.5 h;

Steps:

1.1.A

Nipecotic acid (25 g, 193.79 mmol, 1 equiv.) was taken in a round bottomed flask. To this, sodium carbonate (61.62 g, 581.3 mmol, 3 equiv.) and water (250 mL) were added. The solution was kept in an ice bath and stirred for 10 minutes. To this solution, benzenesulfonyl chloride (41.04 g, 29.8 mL, 232.54 mmol, 1.2 equiv.) was added at 0 ⁰C to 5 ⁰C. After addition, the reaction mixture was stirred at room temperature for 16h. After overnight stirring, TLC was checked for completion of the reaction. The reaction mixture was diluted with water (200 mL) and washed with ethyl acetate. The aqueous layer was collected and acidified with dil HCl upto pH 3 at 0 ⁰C to 5 ⁰C, and was stirred for 15-30 minutes. White solid was obtained, which was filtered, washed with petroleum ether and dried in air and then in vacuo till constant weight to furnish the desired compound. (5 Ig, 97.83%). IH NMR (CDCl₃, 400 MHz): δ 7.77 (d, J= 8 Hz, 2H); 7.63-7.52 (m, 3H); 3.83 (dd, J = 2.8, 8.8 Hz, IH); 3.60 (d, J = 11.6 Hz, IH); 2.71-2.64 (m, IH); 2.57 (t, J = 1 1.2 Hz, IH); 2.40 (dt, J = 2.8 Hz, 10.8 Hz, IH); 2.03-1.99 (m, IH); 1.84-1.79 (IH, m); 1.72- 1.61 (IH, m); 1.47-1.46 (IH, m).

References:

WO2008/87654,2008,A2 Location in patent:Page/Page column 24-25