Water → 1-tert-butyl 4-ethyl 4-(3-(2-oxo-1,8-naphthyridin-1(2H)-yl)propyl)piperidine-1,4-dicarboxylate

HRID 1510649Notes

Reaction equation

HRID 1510649 reaction equation
[NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][N:9]=2)[CH:4]=[CH:3][C:2]1=[O:11].[H-].[Na+].CS(O[CH2:19][CH2:20][CH2:21][C:22]1([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)(=O)=O.O>CN(C)C=O.C(OCC)(=O)C>[O:11]=[C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[N:9][CH:8]=[CH:7][CH:6]=2)[N:1]1[CH2:19][CH2:20][CH2:21][C:22]1([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2996431,8-Naphthyridin-2(1H)-oneHCID 578155261-Tert-butyl 4-ethyl 4-(3-((methanesulfonyl)oxy)propyl)piperidine-1,4-dicarboxylate

Product 1

HCID 578155171-tert-butyl 4-ethyl 4-(3-(2-oxo-1,8-naphthyridin-1(2H)-yl)propyl)piperidine-1,4-dicarboxylateYield 63.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
57.5 °C

Procedure

To a solution of 0.15 g of 1,8-naphthyridin-2(1H)-one in 2 mL of N,N-dimethylformamide, 45 mg of 60% sodium hydride was added, and the mixture was stirred at 50 to 65° C. for 1 hour. Thereto was added a solution of 0.44 g of 1-tert-butyl 4-ethyl 4-(3-((methylsulfonyl)oxy)propyl)piperidine-1,4-dicarboxylate in 1.2 mL of N,N-dimethylformamide, and the reaction mixture was stirred at 80 to 90° C. for 1 hour 30 minutes and cooled to room temperature, and water and ethyl acetate were then added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of hexane:ethyl acetate=3:2 to obtain 0.29 g of 1-tert-butyl 4-ethyl 4-(3-(2-oxo-1,8-naphthyridin-1(2H)-yl)propyl)piperidine-1,4-dicarboxylate as a colorless oily substance.

Workup

  1. stirringthe reaction mixture was stirred at 80 to 90° C. for 1 hour 30 minutes
  2. temperaturecooled to room temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washthe resultant solution was washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe resultant residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-33d79f687d7e46d4a2cf578fc9fd5c27
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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