Toluene-4-sulfonic acid 1-acetyl-piperidin-4-ylMethyl ester synthesis

Yield:846057-25-8 63%

Reaction Conditions:

with dmap;triethylamine in dichloromethane at 0 - 20; for 1 h;

Steps:

11.1

Et3N (0.16 g, 1.60 mmol) and DMAP (0.39 g, 0.32 mmol) were added to a solution of methyl 4-(hy- droxymethyl)piperidine-1-carboxylate (1.0 g, 3.20 mmol) in DCM (20 mE). The reaction mixture was cooled to 00 C. and TsC1 (0.73 g, 3.80 mmol) was added. The reaction mixture was stirred for 1 hat room temperature, diluted with EtOAc, washed with water, dried over anhydrous Na2504 and concentrated under reduced pressure. Purification by flash chromatography (50% EtOAc:hexane) gave (1 -acetylpiperidin-4- yl)methyl 4-methylbenzenesulfonate as a pale yellow semisolid.Yield (1.2 g, 63%); ‘H NMR (400 MHz, CDC13); ? 7.77 (d, J=8.4 Hz, 2H), 7.63 (d, J=7.6 Hz, 2H), 4.64 (d, J=14.4 Hz, 2H), 3.92 (dd, J=6.0, 2.4 Hz, 2H), 3.84 (t, J=3.2 Hz, 4H), 3.02 (d, J=13.6 Hz, 2H), 2.54-2.49 (m, 2H), 2.45 (s, 3H), 1.72-1.62 (m, 1H), 1.16 (dt, J=12.4, 3.6 Hz, 1H); MS: m/z 312.05 [M+H]+.

References:

US2014/275043,2014,A1 Location in patent:Paragraph 0465