Ethanol → Ethyl 4-(1-methylpiperid-4-yloxy)acetoacetate

HRID 1905711Notes

Reaction equation

HRID 1905711 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]1.Cl[CH2:12][C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].C(O)C>CN(C)C=O>[CH3:10][N:7]1[CH2:8][CH2:9][CH:4]([O:3][CH2:12][C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 702EthanolHCID 24758Sodium hydrideHCID 660484-Piperidinol, 1-methyl-HCID 69484Ethyl 4-chloroacetoacetate

Product 1

HCID 20214984Ethyl 4-(1-methylpiperid-4-yloxy)acetoacetateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (5.0 g of 50% dispersion in mineral oil) was added portionwise to a stirred solution of 4-hydroxy-1-methyl-piperidine (11.5 g) in dry dimethylformamide (80 ml). The mixture was stirred at room temperature for 1 hour and then cooled to 10° C. A solution of ethyl 4-chloroacetoacetate (8.2 g) in dry dimethylformamide (20 ml) was added dropwise with stirring and stirring was continued for a further 20 hours at room temperature. Ethanol (10 ml) was added and the solution was evaporated to dryness. The residue was partitioned between dichloromethane and dilute hydrochloric acid. The organic layer was separated, dried over sodium sulphate and evaporated to given an oil which was partitioned between acetonitrile and petrol to remove mineral oil. The acetonitrile extract was evaporated to give the title compound as an oil (10.3 g) which was used without further purification.

Workup

  1. temperaturecooled to 10° C
  2. stirringwith stirring
  3. stirringstirring
  4. waitwas continued for a further 20 hours at room temperature
  5. customthe solution was evaporated to dryness
  6. customThe residue was partitioned between dichloromethane and dilute hydrochloric acid
  7. customThe organic layer was separated
  8. dry with materialdried over sodium sulphate
  9. customevaporated
  10. customwas partitioned between acetonitrile and petrol
  11. customto remove mineral oil
  12. extractionThe acetonitrile extract
  13. customwas evaporated

Sources & evidence

ORD record
ord-f7a8ebb3337e4634b49c8d3daef5cc8c
Source dataset
uspto-grants-1987_03
Patent number
US04647565

Reaction notes

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