Citric Acid → tert-Butyl 1-(piperidine-1-carbonyl)piperidin-4-ylcarbamate

HRID 915890Notes

Reaction equation

HRID 915890 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH2:3]1.ClC(Cl)(O[C:20](=[O:26])OC(Cl)(Cl)Cl)Cl.[NH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.C(N(CC)CC)C>[N:28]1([C:20]([N:2]2[CH2:3][CH2:4][CH:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH2:6][CH2:7]2)=[O:26])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 8082PiperidineHCID 94429TriphosgeneHCID 27560284-(tert-Butoxycarbonylamino)piperidine hydrochloride

Product 1

HCID 53256232tert-Butyl 1-(piperidine-1-carbonyl)piperidin-4-ylcarbamateYield 100.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

A suspension of 1.0 g of tert-butyl piperidin-4-ylcarbamate hydrochloride and 0.6 ml of triethylamine in 15 ml of methylene chloride was added to a solution of 418 mg of triphosgene in 10 ml of methylene chloride under cooling with ice-water bath. The reaction mixture was stirred for 2 hours with ice cooling, and then a solution of 358 mg of piperidine and 0.6 ml of triethylamine in 5 ml of methylene chloride was added thereto and stirred at room temperature for 15 hours. Aqueous 10% citric acid solution was added to the reaction mixture, and this was extracted with EtOAc. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting solid was washed with ether to obtain 440 mg of tert-butyl [1-(piperidine-1-carbonyl)piperidin-4-yl]carbamate.

Workup

  1. temperatureunder cooling with ice-water bath
  2. stirringstirred at room temperature for 15 hours
  3. extractionthis was extracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. washThe resulting solid was washed with ether

Sources & evidence

ORD record
ord-dd3333c7c1684567af2e10d34c6c0157
Source dataset
uspto-grants-2007_09
Patent number
US07268150B2

Reaction notes

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