Trifluoroacetohydrazide → Ethyl 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate

HRID 62474Notes

Reaction equation

HRID 62474 reaction equation
S=[C:2]1[CH2:7][CH:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:5][CH2:4][NH:3]1.[F:13][C:14]([F:20])([F:19])[C:15]([NH:17][NH2:18])=O>C1COCC1.[Hg](OC(C)=O)OC(C)=O>[F:13][C:14]([F:20])([F:19])[C:15]1[N:3]2[CH2:4][CH2:5][CH:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][C:2]2=[N:18][N:17]=1

Participants

5

Reactant 2

HCID 229753TrifluoroacetohydrazideHCID 90303563Ethyl 2-thioxopiperidine-4-carboxylate

Product 1

HCID 90304476Ethyl 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylateYield 88.9%

Reagents, catalysts & solvents 2

HCID 16683746DiacetyloxymercuryCatalystHCID 8028TetrahydrofuranSolvent

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).

Workup

  1. temperatureheated at 60° C. for overnight
  2. filtrationfiltered
  3. customRemoved the solvent under reduced pressure
  4. concentrationthe filtrate was concentrated
  5. custompurified by silica gel column chromatography (PE/EA=3/1)

Sources & evidence

ORD record
ord-267e07dbb5154f9fbe390e4ebde26203
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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