Acetyl chloride → 1-(4-Aminopiperidin-1-yl)ethan-1-one

HRID 2093919Notes

Reaction equation

HRID 2093919 reaction equation
C(OC([C:8]1([NH2:14])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.[C:24](Cl)(=[O:26])[CH3:25].FC(F)(F)C(O)=O>ClCCl>[NH2:14][CH:8]1[CH2:9][CH2:10][N:11]([C:24](=[O:26])[CH3:25])[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 66867394HCID 66867394, compound

Product 1

HCID 49624771-(4-Aminopiperidin-1-yl)ethan-1-oneYield 55.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-amino-piperidine-4-carboxylic acid tert-butyl ester (2.50 g; 12.5 mmol) and Huenigs base (3.2 mL) in dichloromethane (15 mL) is added acetyl chloride (1.1 mL; 15.0 mmol) under ice-cooling. The mixture is stirred overnight at ambient temperature. The solvent is evaporated and the obtained crude is partitioned between ethyl acetate and 1M aqueous HCl. Drying and evaporation of the solvent gave an orange oil which is dissolved in dichloromethane (38 mL). Trifluoroacetic acid (19 mL) is added and the mixture is stirred for 20 min at ambient temperature. The volatiles are completely evaporated at 35° C. bath temperature and the obtained residue is dissolved in a mixture of dichloromethane/methanol (95:5 v/v). Solid sodium carbonate is added and the suspension is stirred at ambient temperature overnight. Filtration and evaporation of the solvent gave 0.98 g of the title compound as slightly brown oil.

Workup

  1. temperaturecooling
  2. customThe solvent is evaporated
  3. customthe obtained crude
  4. customis partitioned between ethyl acetate and 1M aqueous HCl
  5. customDrying
  6. customevaporation of the solvent
  7. customgave an orange oil which
  8. stirringthe mixture is stirred for 20 min at ambient temperature
  9. customThe volatiles are completely evaporated at 35° C. bath temperature
  10. dissolutionthe obtained residue is dissolved in a mixture of dichloromethane/methanol (95:5 v/v)
  11. additionSolid sodium carbonate is added
  12. stirringthe suspension is stirred at ambient temperature overnight
  13. filtrationFiltration and evaporation of the solvent

Sources & evidence

ORD record
ord-aca6d8af8dcc4fd1be36009464cb31e4
Source dataset
uspto-grants-2013_05
Patent number
US08445501B2

Reaction notes

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