Benzyl chloroformate → 3-Benzyloxycarbonylamino-6-propyl-2-pyridinone

HRID 1600072Notes

Reaction equation

HRID 1600072 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[NH2:12][C:13]1[C:14](=[O:22])[NH:15][C:16]([CH2:19][CH2:20][CH3:21])=[CH:17][CH:18]=1>O1CCOCC1.[OH-].[Na+].O.C(=O)(O)[O-].[Na+]>[CH2:5]([O:4][C:2]([NH:12][C:13]1[C:14](=[O:22])[NH:15][C:16]([CH2:19][CH2:20][CH3:21])=[CH:17][CH:18]=1)=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

7

Reactant 2

HCID 10387Benzyl chloroformate2×HCID 212245473-amino-6-propyl-2(1H)-Pyridinone

Product 1

HCID 212245233-Benzyloxycarbonylamino-6-propyl-2-pyridinoneYield 85.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Benzyl chloroformate (1.8 ml, 12.6 mmol) was added to a solution of 3-amino-6-propyl-2-(1H)-pyridinone (1.63 g, 10.8 mmol) in a mixture of dioxane (25 ml) and IN NaOH at 0° C. Within minutes a white precipitate formed. The reaction mixture was stirred at the same temperature for 1 hr then at room temperature for an additional hour. The reaction mixture was diluted with water and extracted with ethyl acetate then methylene chloride. Each extract was washed with brine then combined and dried over magnesium sulfate. Removal of the solvents in vacuo gave a yellow semi-solid which was a mixture of starting material and product. This was redissolved in a mixture of dioxane (24 ml) and 10% aqueous sodium bicarbonate (12 ml) and cooled to 0° C. Benzyl chloroformate(1.5 ml, 10.5 mmol) was once again added and after stirring for 30 min, thereaction mixture was allowed to stir at room temperature for 3 h. After dilution with water, the precipitate was filtered off and washed thoroughly, first with water and then with ether. Drying gave 2.64 g of the title compound as a white powder: 1H NMR (CDCl3) δ0.96 (t, J=7.3 Hz, 3 H), 1.68 (m, 2 H), 2.52 (t, J=7.5 Hz, 2 H), 5.22 (s, 2 H), 6.07 (d, J=7.5 Hz, 1 H), 7.34-7.43 (m, 4 H), 7.68 (s, 1 H),8.05 (brd,J=5.3Hz, 1H).

Workup

  1. customWithin minutes a white precipitate formed
  2. waitat room temperature for an additional hour
  3. extractionextracted with ethyl acetate
  4. washEach extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customRemoval of the solvents in vacuo
  7. customgave a yellow semi-solid which
  8. additiona mixture of starting material and product
  9. stirringafter stirring for 30 min
  10. stirringto stir at room temperature for 3 h
  11. filtrationAfter dilution with water, the precipitate was filtered off
  12. washwashed thoroughly, first with water
  13. customDrying

Sources & evidence

ORD record
ord-e58bbf0b4c8c4e3e904dac8290a5eeea
Source dataset
uspto-grants-1998_04
Patent number
US05744486

Reaction notes

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