Ethyl trifluoroacetate → Tert-butyl 3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(trifluoroacetyl)amino)methyl)piperidine-1-carboxylate

HRID 385559Notes

Reaction equation

HRID 385559 reaction equation
[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][NH:12][CH2:13][CH:14]3[CH2:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]3)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1.[F:27][C:28]([F:35])([F:34])[C:29](OCC)=[O:30]>CO>[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][N:12]([CH2:13][CH:14]3[CH2:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]3)[C:29](=[O:30])[C:28]([F:35])([F:34])[F:27])[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 9794Ethyl trifluoroacetate2×HCID 57815295Tert-butyl 3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)piperidine-1-carboxylate

Product 1

HCID 57815322Tert-butyl 3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(trifluoroacetyl)amino)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1.3 g of tert-butyl 3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)piperidine-1-carboxylate in 10 mL of methanol, 0.54 mL of ethyl trifluoroacetate was added, and a mixture was stirred at room temperature for 2 hours, and then stirred at 40 to 45° C. for 3 hours. Thereto was added 0.54 mL of ethyl trifluoroacetate, and the mixture was heated under reflux while stirring for 3 hours. The mixture was cooled to room temperature, and the solvent was then distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of hexane:ethyl acetate=1:1 to obtain 0.47 g of tert-butyl 3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(trifluoroacetyl)amino)-methyl)piperidine-1-carboxylate as a colorless oily substance.

Workup

  1. stirringstirred at 40 to 45° C. for 3 hours
  2. temperaturethe mixture was heated
  3. temperatureunder reflux
  4. stirringwhile stirring for 3 hours
  5. temperatureThe mixture was cooled to room temperature
  6. distillationthe solvent was then distilled off under reduced pressure
  7. customThe resultant residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-88c262e5b340433d9d998ed8641d8599
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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