ethyl 2-sulfanylidenepiperidine-4-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-thioxopiperidine-4-carboxylate (5.7 g, 14.95 mmol) in THF (203 mL) was added 2,2,2-trifluoroacetohydrazide (7.8 g, 60.88 mmol) and Hg(OAc)2 (10.71 g, 33.48 mmol) at ice-water. The mixture was stirred at room temperature for 2 hours and heated at 60° C. for overnight, then filtered. Removed the solvent under reduced pressure and the filtrate was concentrated and purified by silica gel column chromatography (PE/EA=3/1) to afford ethyl 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (3.5 g, yield 43.8%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.10-1.32 (m, 3H) 2.16 (br. s., 1H) 2.36 (br. s., 1H) 2.93 (br. s., 1H) 3.02-3.39 (m, 2H) 3.90-4.30 (m, 4H). heated at 60° C. for overnight filtered Removed the solvent under reduced pressure the filtrate was concentrated purified by silica gel column chromatography (PE/EA=3/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-oxopiperidine-4-carboxylate (10.76 g, 62.85 mmol) in toluene (120 mL) was added the Lawesson's reagent (25.42 g, 62.85 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 2 h. Removed the solvent under reduced pressure and the residue was purified by silica gel column chromatography (DCM/EA=20/1) to afford ethyl 2-thioxopiperidine-4-carboxylate (5.8 g, yield 49.3%). The mixture was heated to reflux for 2 h Removed the solvent under reduced pressure the residue was purified by silica gel column chromatography (DCM/EA=20/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-thioxopiperidine-4-carboxylate (5.7 g, 14.95 mmol) in THF (203 mL) was added 2,2,2-trifluoroacetohydrazide (7.8 g, 60.88 mmol) and Hg(OAc)2 (10.71 g, 33.48 mmol) at ice-water. The mixture was stirred at room temperature for 2 hours and heated at 60° C. for overnight, then filtered. Removed the solvent under reduced pressure and the filtrate was concentrated and purified by silica gel column chromatography (PE/EA=3/1) to afford ethyl 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (3.5 g, yield 43.8%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.10-1.32 (m, 3H) 2.16 (br. s., 1H) 2.36 (br. s., 1H) 2.93 (br. s., 1H) 3.02-3.39 (m, 2H) 3.90-4.30 (m, 4H). heated at 60° C. for overnight filtered Removed the solvent under reduced pressure the filtrate was concentrated purified by silica gel column chromatography (PE/EA=3/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-oxopiperidine-4-carboxylate (10.76 g, 62.85 mmol) in toluene (120 mL) was added the Lawesson's reagent (25.42 g, 62.85 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 2 h. Removed the solvent under reduced pressure and the residue was purified by silica gel column chromatography (DCM/EA=20/1) to afford ethyl 2-thioxopiperidine-4-carboxylate (5.8 g, yield 49.3%). The mixture was heated to reflux for 2 h Removed the solvent under reduced pressure the residue was purified by silica gel column chromatography (DCM/EA=20/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-thioxopiperidine-4-carboxylate (5.7 g, 14.95 mmol) in THF (203 mL) was added 2,2,2-trifluoroacetohydrazide (7.8 g, 60.88 mmol) and Hg(OAc)2 (10.71 g, 33.48 mmol) at ice-water. The mixture was stirred at room temperature for 2 hours and heated at 60° C. for overnight, then filtered. Removed the solvent under reduced pressure and the filtrate was concentrated and purified by silica gel column chromatography (PE/EA=3/1) to afford ethyl 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (3.5 g, yield 43.8%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.10-1.32 (m, 3H) 2.16 (br. s., 1H) 2.36 (br. s., 1H) 2.93 (br. s., 1H) 3.02-3.39 (m, 2H) 3.90-4.30 (m, 4H). heated at 60° C. for overnight filtered Removed the solvent under reduced pressure the filtrate was concentrated purified by silica gel column chromatography (PE/EA=3/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-oxopiperidine-4-carboxylate (10.76 g, 62.85 mmol) in toluene (120 mL) was added the Lawesson's reagent (25.42 g, 62.85 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 2 h. Removed the solvent under reduced pressure and the residue was purified by silica gel column chromatography (DCM/EA=20/1) to afford ethyl 2-thioxopiperidine-4-carboxylate (5.8 g, yield 49.3%). The mixture was heated to reflux for 2 h Removed the solvent under reduced pressure the residue was purified by silica gel column chromatography (DCM/EA=20/1)