Potassium Carbonate → 4-Acetamido-1-[6-(2,2,2-trifluoro) ethoxy-2-pyridyl]piperidine

HRID 647513Notes

Reaction equation

HRID 647513 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[N:3]=1.[CH:14]([NH:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:15].[CH:23](NC1CCN(CC2C=CC=CC=2)CC1)=O.C(=O)([O-])[O-].[K+].[K+]>[Pd].S1(CCCC1)(=O)=O.[Cu]>[C:14]([NH:16][CH:17]1[CH2:22][CH2:21][N:20]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[N:3]=2)[CH2:19][CH2:18]1)(=[O:15])[CH3:23]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 12760119HCID 12760119, compoundHCID 14593334HCID 14593334, compoundHCID 18695554HCID 18695554, compound

Product 1

HCID 129266194-Acetamido-1-[6-(2,2,2-trifluoro) ethoxy-2-pyridyl]piperidine

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 23978CopperCatalystHCID 31347SulfolaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 19 g of 2-chloro-6-(2,2,2-trifluoroethoxy)pyridine (b.p. 80° C./16 mm Hg, prepared by reaction of 2,6-dichloropyridine with 2,2,2-trifluoroethanolate of sodium), 14.87 g of 4-formamidopiperidine (m.p. 116° to 118° C., prepared by hydrogenation of 4-formamido-1-benzylpiperidine in the presence of palladium on charcoal), 17.27 g of anhydrous potassium carbonate, 5.67 g of copper in powder form in 110 ml of sulfolane is heated to 100° C. with stirring for 50 hours, then the sulfolane is distilled, the residue is taken up with water and the suspension thus obtained is extracted with methylene chloride. The organic phase is washed with water, it is dried over anhydrous sodium sulfate and evaporated to dryness. The residue, firstly crystallised in an 84/16 by volume mixture of water/ethanol and afterwards in diisopropylic ether, gives 9 g of 4-acetamido-1-[6-(2,2,2-trifluoro)ethoxy-2-pyridyl] piperidine; m.p. 92° to 95° C.

Workup

  1. distillationthe sulfolane is distilled
  2. customthe suspension thus obtained
  3. extractionis extracted with methylene chloride
  4. washThe organic phase is washed with water, it
  5. dry with materialis dried over anhydrous sodium sulfate
  6. customevaporated to dryness
  7. customThe residue, firstly crystallised in an 84/16 by volume mixture of water/ethanol and afterwards in diisopropylic ether

Sources & evidence

ORD record
ord-abc52f84b510419bb52e0236742574fe
Source dataset
uspto-grants-1983_10
Patent number
US04409228

Reaction notes

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