[1-(Phenylsulphonyl)piperidin-3-yl]methanol synthesis

Yield:346691-49-4 91.4%

Reaction Conditions:

Stage #1: 1-benzenesulfonyl-piperidine-3-carboxylic acid methyl esterwith lithium aluminium tetrahydride in tetrahydrofuran at 0 - 20;
Stage #2: with potassium hydroxide in tetrahydrofuran;water at 0;

Steps:

1.1.C

The methyl ester (51 g, 180.2 mmol, 1 equiv.) from above, was dissolved in dry THF (500 mL) and transferred into pressure equalizing funnel. Lithium aluminum hydride (8.2 Ig, 216.2 mmol, 1.2 equiv.) was suspended in dry THF (100 mL) in a round bottomed flask (1 L). The ester from dropping funnel was added dropwise at 0 ⁰C to 5 ⁰C. After the complete addition, the reaction mixture was brought to room temperature and stirred. The reaction was monitored by TLC till completion. The reaction mixture was cooled to 0 ⁰C and carefully quenched with slow addition of aqueous KOH (IN). Gray colored free flowing solid was separated; ethyl acetate (500 mL) was added and then solid was filtered through hyflour using sintered disk. The filtrate was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to furnish the title compound (42g, 91.4%).IH NMR (CDCl₃, 400 MHz): δ 7.77 (d, J= 8 Hz, 2H); 7.62-7.52 (m, 3H); 3.65 (dd, J = 2.8, 11.2 Hz, IH); 3.59-3.49 (m, 3H); 2.46 (t, J = 10.8 Hz, IH); 2.30 (t, J = 10.4 Hz, IH); 1.93-1.63 (m, 5H); 01.14-0.94 (m, IH).

References:

WO2008/87654,2008,A2 Location in patent:Page/Page column 25-26