Methanol → Ethyl 3-(4-chlorophenyl)-2-(4-((dimethylamino)methyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 1467740Notes

Reaction equation

HRID 1467740 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:22]=[CH:21][C:8](/[CH:9]=[N:10]/[C:11]2[CH:19]=[CH:18]C=C3[C:12]=2[CH2:13][O:14]C3=O)=[CH:7][CH:6]=1)[CH3:3].[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1.C[O-].[Na+].CO.[C:37]([O:41][CH2:42][CH3:43])(=[O:40])[CH2:38][CH3:39]>>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]2[C:13](=[O:14])[C:12]3[C:38]([C:37]([O:41][CH2:42][CH3:43])=[O:40])=[CH:39][CH:18]=[CH:19][C:11]=3[NH:10][CH:9]2[C:8]2[CH:7]=[CH:6][C:5]([CH2:4][N:2]([CH3:3])[CH3:1])=[CH:22][CH:21]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 5

HCID 887MethanolHCID 77264-ChlorobenzaldehydeHCID 7749Ethyl PropionateHCID 10942334Sodium MethoxideHCID 178483208HCID 178483208, compound

Product 1

HCID 67258647Ethyl 3-(4-chlorophenyl)-2-(4-((dimethylamino)methyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateYield 28%

Conditions

Temperature
0 °C

Procedure

A mixture of (E)-4-(4-((dimethylamino)methyl)benzylideneamino)isobenzofuran-1(3H)-one (588 mg, 2 mmol) and 4-chlorobenzaldehyde (281 mg, 2 mmol) in anhydrous ethyl propionate (25 mL) was cooled to 0° C. The sodium methoxide in methanol solution (sodium (115 mg, 5 mmol) in anhydrous ethanol (10 mL)) was added dropwise and the mixture was stirred at 25° C. for 3 hr. The resulting mixture was quenched with water (5 mL), and then evaporated under reduced pressure. The residue was extracted with ethyl acetate (100 mL×3) and the combined organic layers were dried over anhydrous sodium sulfate and concentrated to give crude product, which was purified by column chromatography (silica gel, dichloromethane to dichloromethane/methanol=30:1) to give the title compound (260 mg, yield 28%) as a yellow solid. LC-MS (ESI) m/z: 463 (M+1)+.

Workup

  1. customThe resulting mixture was quenched with water (5 mL)
  2. customevaporated under reduced pressure
  3. extractionThe residue was extracted with ethyl acetate (100 mL×3)
  4. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give crude product, which
  7. customwas purified by column chromatography (silica gel, dichloromethane to dichloromethane/methanol=30:1)

Sources & evidence

ORD record
ord-3091a15696b74c1ab0d97e878f7def08
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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