Citric Acid → HCID 59718785, compound

HRID 1925619Notes

Reaction equation

HRID 1925619 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:5]=2[CH:4]=[C:3]1[C:14]([O:16][CH3:17])=[O:15].[H-].[Na+].[C:20]([C:22]1[CH:29]=[CH:28][C:25]([CH2:26]N)=[CH:24][CH:23]=1)#[N:21].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.O>[C:20]([C:22]1[CH:29]=[CH:28][C:25]([CH2:26][N:7]2[C:2](=[O:1])[C:3]([C:14]([O:16][CH3:17])=[O:15])=[CH:4][C:5]3[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][C:6]2=3)=[CH:24][CH:23]=1)#[N:21]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 826084-(Aminomethyl)benzonitrileHCID 67520042HCID 67520042, compound

Product 1

HCID 59718785HCID 59718785, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under the nitrogen gas atmosphere, methyl 2-oxo-1,2,5,6,7,8,9,10-octahydro-cycloocta[b]pyridine-3-carboxylate (300 mg, 1.27 mmol) was dissolved in DMF (5 mL), sodium hydride (61 mg, 1.53 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After that, 4-cyanobenzylamine (274.9 mg, 1.40 mmol) was added, and the mixture was further stirred at room temperature for 1 hour. Subsequently, water and 5% citric acid were added to the reaction mixture, and the obtained mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was refined with silica gel (10 g) column chromatography (ethyl acetate-hexane of 1:1 in mixing ratio), and colorless solid of methyl 1-(4-cyanobenzyl)-2-oxo-1,2,5,6,7,8,9,10-octahydro-cycloocta[b]pyridine-3-carboxylate (AA04, 100 mg, 22%, mp: 72-75° C.) and colorless solid of methyl 2-(4-cyanophenoxy)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridine-3-carboxylate (123 mg, 28%, mp: 122-123° C.) were obtained.

Workup

  1. stirringthe mixture was further stirred at room temperature for 1 hour
  2. extractionthe obtained mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried with anhydrous sodium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. additionthe residue was refined with silica gel (10 g) column chromatography (ethyl acetate-hexane of 1:1 in mixing ratio), and colorless solid of methyl 1-(4-cyanobenzyl)-2-oxo-1,2,5,6,7,8,9,10-octahydro-cycloocta[b]pyridine-3-carboxylate (AA04, 100 mg, 22%, mp: 72-75° C.) and colorless solid of methyl 2-(4-cyanophenoxy)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridine-3-carboxylate (123 mg, 28%, mp: 122-123° C.)
  7. customwere obtained

Sources & evidence

ORD record
ord-6d0e2489d6184b28b39cbcabd1f978f5
Source dataset
uspto-grants-2012_05
Patent number
US08178681B2

Reaction notes

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