3-Chloroaniline → HCID 178498504, compound

HRID 1353437Notes

Reaction equation

HRID 1353437 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[C:9]([C:15](OC)=[O:16])#[C:10][C:11]([O:13][CH3:14])=[O:12]>CO>[CH3:14][O:13][C:11]([C:10]1[CH:9]=[C:15]([OH:16])[C:6]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:8][CH:7]=2)[N:5]=1)=[O:12]

Participants

4

Reactant 2

HCID 79323-ChloroanilineHCID 12980Dimethyl acetylenedicarboxylate

Product 1

HCID 178498504HCID 178498504, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 3-chloroaniline (40.8 g, 320 mmol) in MeOH (500 mL) at rt was added dimethyl acetylene dicarboxylate (50 g, 352 mmol). After addition, the reaction was kept at reflux for 2 h, then cooled to rt. After evaporating methanol in vacuo, the resulting crude adduct was dissolved in Ph2O (160 mL), and was added dropwise to a hot solution of Ph2O (800 mL) in a three-neck flask at 250° C. The reaction mixture was kept at 250° C. for an additional 30 min, and was cooled to rt. The reaction mixture was diluted with hexane, and the product precipitated. The crude mixture was collected by filtration (washed with hexane and ether). This mixture (78 g) was re-dissolved in pyridine (468 mL) (Note: the other solvent for re-crystallization is acetic acid, and the ratio of crude product to acetic acid is 1:6 based on weight), and kept at reflux for about 30 min. After cooling to rt, the desired product was collected by filtration (washed with ether). The solid was air dried overnight to give 35 g (46%) of 7-chloro-4-hydroxy-2-quinolinecarboxylic acid methyl ester. LC-MS: 237 (M++1). 1H NMR (DMSO-d6): 63.98 (s, 3H), 6.6 (s, 1), 7.38 (d, 1H), 7.96 (s, 1H), 8.04 (d, 1), 12.1 (s, 1).

Workup

  1. additionAfter addition
  2. temperatureat reflux for 2 h
  3. customAfter evaporating methanol in vacuo
  4. dissolutionthe resulting crude adduct was dissolved in Ph2O (160 mL)
  5. additionwas added dropwise to a hot solution of Ph2O (800 mL) in a three-neck flask at 250° C
  6. temperaturewas cooled to rt
  7. additionThe reaction mixture was diluted with hexane
  8. customthe product precipitated
  9. filtrationThe crude mixture was collected by filtration (washed with hexane and ether)
  10. dissolutionThis mixture (78 g) was re-dissolved in pyridine (468 mL) (Note
  11. customthe other solvent for re-crystallization
  12. temperatureat reflux for about 30 min
  13. temperatureAfter cooling to rt
  14. filtrationthe desired product was collected by filtration (washed with ether)
  15. customdried overnight

Sources & evidence

ORD record
ord-343250b313b34500b3a91518c10f57e4
Source dataset
uspto-grants-2007_05
Patent number
US07220856B2

Reaction notes

Loading…