Toluene → HCID 23542035, compound

HRID 1591642Notes

Reaction equation

HRID 1591642 reaction equation
[CH3:1][O:2][C:3](=[O:10])[CH2:4][C:5]([CH:7]1[CH2:9][CH2:8]1)=O.C([O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:21])C.[C:23]1(C)C=CC=CC=1>C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:2][C:3]([C:4]1[C:14](=[O:13])[C:15]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[NH:21][C:5]=1[CH:7]1[CH2:9][CH2:8]1)=[O:10])[CH3:23]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6877Ethyl 2-aminobenzoateHCID 101300163-Cyclopropyl-3-Oxopropionic Acid Methyl Ester

Product 1

HCID 23542035HCID 23542035, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6101p-Toluenesulfonic acidCatalyst

Conditions

Temperature
120 °C

Procedure

A solution of 3-cyclopropyl-3-oxo-propionic acid methyl ester (6.2 g, 0.038 mols), 2-amino benzoic acid ethyl ester (4.95 g, 0.03 mols) and p-toluene sulfonic acid (0.04 g, 0.2 mmols) in toluene (25 ml) was heated at 125° C. for 2 h; 15 ml of solvent was then distilled. To the residual orange solution was added sodium ethoxide (2 M, 15 ml) in ethanol (reaction mixture turns red). This red mixture was stirred at 120° C. for 2 h; 15 ml of solvent was again distilled. The reaction mixture was left to cool to room temperature, diluted with ethyl acetate (1 litre), extracted with HCl 0.1 M and water. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to leave an orange residue which was washed once with cold ethyl acetate to yield 2-cyclopropyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester (3.87 g, 53%) as an off-white solid. LCMS m/z 244.14 [M+H]+ @ RT 0.78 min, 89%, m/z 230.11 [Acid+H]+ @ RT 1.27, 11%. δH (400 MHz, (CD3)2SO) 11.04 (1H, s), 8.06 (1H, dd, J1 1.1, J2 8.1), 7.76-7.66 (2H, m), 7.36 (1H, td, J1 1.1, J2 7.5), 3.89 (3H, s), 2.16 (1H, m), 1.18 (4H, d, J 7.0). Step 2 4-Chloro-2-cyclopropyl-quinoline-3-carboxylic acid ethyl ester

Workup

  1. distillation15 ml of solvent was then distilled
  2. additionTo the residual orange solution was added sodium ethoxide (2 M, 15 ml) in ethanol (reaction mixture turns red)
  3. distillation15 ml of solvent was again distilled
  4. waitThe reaction mixture was left
  5. temperatureto cool to room temperature
  6. additiondiluted with ethyl acetate (1 litre)
  7. extractionextracted with HCl 0.1 M and water
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto leave an orange residue which
  11. washwas washed once with cold ethyl acetate

Sources & evidence

ORD record
ord-648660a0cac740eb90dbcbb56765b582
Source dataset
uspto-grants-2007_11
Patent number
US07291612B2

Reaction notes

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