Benzaldehyde → HCID 67258928, compound

HRID 1967884Notes

Reaction equation

HRID 1967884 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][O:5][C:6]2=[O:11].[CH:12](=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:20][O-:21].[Na+].CO.[C:25]([O:29][CH2:30][CH3:31])(=[O:28])[CH2:26][CH3:27]>>[O:29]=[C:25]1[C:3]2[C:7]([C:6]([O:5][CH3:4])=[O:11])=[CH:8][CH:9]=[CH:10][C:2]=2[NH:1][CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:26]1[C:27]1[CH:9]=[CH:10][CH:2]=[CH:3][CH:4]=1.[O:21]=[C:20]1[C:10]2[C:26]([C:25]([O:29][CH2:30][CH3:31])=[O:28])=[CH:27][CH:4]=[CH:3][C:2]=2[NH:1][CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:4]1[C:3]1[CH:2]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 887MethanolHCID 7749Ethyl PropionateHCID 10942334Sodium MethoxideHCID 122846494-Amino-1,3-dihydro-2-benzofuran-1-one

Product 2

HCID 67258790HCID 67258790, compoundYield 14%HCID 67258928HCID 67258928, compoundYield 27%

Conditions

Temperature
0 °C

Procedure

A mixture of 4-aminoisobenzofuran-1(3H)-one (0.4 g, 2.68 mmol) and benzaldehyde (0.72 g, 6.7 mmol) in ethyl propionate (20 mL) was cooled to 0° C. Then a solution of sodium methoxide in methanol [sodium (248 mg, 10.72 mmol) in methanol (20 mL)] was added dropwise. After the addition, the mixture was heated at reflux for 16 hr. The mixture was quenched with water (10 mL) and solvent was removed in vacuum. The residue was dissolved in water, acidified with 1N hydrochloric acid to pH=6, then extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by prep-HPLC to give methyl 4-oxo-2,3-diphenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (256 mg, yield 27%) and ethyl 4-oxo-2,3-diphenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (140 mg, yield 14%) as a light yellow solid. Methyl 4-oxo-2,3-diphenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate: MS (ESI) m/z: 358 (M+1)+. 1H-NMR (400 MHz, CDCl3) δ 3.86 (s, 3H), 3.95-3.98 (d, J=16.4 Hz, 1H), 4.81-4.84 (d, J=12.8 Hz, 1H), 4.89 (s, br 1H), 6.72-6.77 (m, 2H), 6.90-6.93 (m, 2H), 7.11-7.21 (m, 8H), 7.34-7.36 (t, J=7.8 Hz, 1H).

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 16 hr
  4. customThe mixture was quenched with water (10 mL) and solvent
  5. customwas removed in vacuum
  6. dissolutionThe residue was dissolved in water
  7. extractionextracted with ethyl acetate (50 mL×3)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customto give crude product
  12. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-3c9b96f2bb8f48b6bcc63987c4d0a551
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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