Hydrochloric Acid → HCID 86635428, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (Ex. 3a, 35.5 g, 0.13 moles) in degassed 2-butanone (400 mL) were added 2,6-di-tert-butyl-4-mercapto-phenol (37.9 g, 0.16 moles) and cesium carbonate (62.7 g, 0.19 moles). The resulting solution was heated to 60° C. and stirred for 8 hours. Upon completion, as determined by HPLC, the reaction was diluted with 400 mL water and 500 mL ethyl acetate. The layers were cut and the organic layer was washed with saturated ammonium chloride solution (400 mL) and brine (400 mL). The volume was then concentrated under reduced pressure to 250 mL. 1,4-Dioxane (300 mL) was added, and then concentrated under reduced pressure to 100 mL. 1,4-Dioxane (300 mL) was added again. HCl (4.0 M in dioxane, 195 mL, 0.7 moles) was added slowly over 30 minutes, and the reaction was stirred at room temperature for 16 hours. The solution was concentrated under reduced pressure to 100 mL, and 1:3 solution of ethyl acetate:hexanes (250 mL) was added while stirring. After 3 hours, the solid was filtered and rinsed with a 1:9 solution of Ethyl acetate:hexanes (80 mL). The wet cake was allowed to air dry, and the solid were added to 120 mL of ethyl acetate and 120 mL of water. A 5.0 N solution of NaOH (28 mL, 0.14 moles) was added to the solution and the reaction was stirred for 30 minutes. The layers were cut. The organic layer was washed with a 6% brine solution (2×100 mL). The solution was concentrated under reduced pressure, and hexanes (70 mL) was added. The mixture was stirred for 16 hours at room temperature, then cooled to −5° C. and stirred for another hour. The solution was filtered and the solid was rinsed with cold hexanes (15 mL) and dried in a vacuum oven for 16 hours, affording 29.5 g (72.2%) of 2,6-di-tert-butyl-4-(piperidin-4-ylsulfanyl)-phenol as a white solid, mp 113-114° C. 1H-NMR (400 MHz, CDCl3): δ7.28 (s, 2H), 5.27 (s, 1H), 3.14-3.09 (m, 2H), 2.98-2.91 (m, 1H), 2.66-2.59 (m, 2H), 1.96-1.92 (m, 2H), 1.51-1.47 (m, 2H), 1.44 (s, 18H). HRMS (ESI) Calcd. for C19H31NOS: 322.2204 ([M+H]+). Found: 322.2196. Anal. Calcd. for C19H31NOS, C, 70.98; H, 9.72; N, 4.36; S, 9.97. Found: C, 70.87; H, 9.76; N, 4.30; S, 9.93.

Provenance & Evidence