Chloroform → 2-Chloro-6,7-difluoro-3-formyl-1,4-dihydroquinoline

HRID 1073595Notes

Reaction equation

HRID 1073595 reaction equation
P(Cl)(Cl)(Cl)=O.Cl[CH:7]([Cl:9])Cl.[F:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[F:21])[NH:17][C:16](=[O:22])[CH2:15][CH2:14]2.C([O-])(=O)C.[Na+]>O.CN(C)C=O>[Cl:9][C:7]1[NH:17][C:18]2[C:13]([CH2:14][C:15]=1[CH:16]=[O:22])=[CH:12][C:11]([F:10])=[C:20]([F:21])[CH:19]=2

Participants

7

Reactant 4

HCID 6212ChloroformHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 148533346,7-Difluoro-3,4-dihydroquinolin-2(1h)-one

Product 1

HCID 148533352-Chloro-6,7-difluoro-3-formyl-1,4-dihydroquinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

76.9 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10° and 15° C., to a mixture of 800 cm3 of trichloromethane and 74.35 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 65.8 g of 6,7-difluoro-3,4-dihydrocarbostyril are added in the course of 10 minutes, at about 20° C., with vigorous stirring, to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and kept at this temperature for 2 hours. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 500 g of ice and 500 cm3 of water is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 3 times 300 cm3 of water at 5° C. The moist product obtained and 60 g of sodium acetate are added simultaneously, in the course of 1 hour, to 1.5 liters of water at 90° C., in such a way as to keep the pH at about 6. The mixture is stirred for a further 30 minutes at 90° C., the temperature is allowed to fall to about 50° C. and the product is drained at this temperature and washed with 3 times 300 cm3 of water at about 20° C. 70.18 g of 2-chloro-6,7-difluoro-3-formyl-1,4-dihydroquinoline are obtained in the form of a yellow solid melting at 260° C., which is used in this form for the subsequent steps.

Workup

  1. customclose to 20° C
  2. customobtained
  3. customThe suspension obtained
  4. temperatureis heated to a temperature
  5. customclose to 60° C.
  6. waitkept at this temperature for 2 hours
  7. concentrationThe reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture
  8. customis obtained
  9. additionis added, with vigorous stirring
  10. customThe solid obtained
  11. customis drained at about 5° C.
  12. washwashed with 3 times 300 cm3 of water at 5° C
  13. customThe moist product obtained
  14. stirringThe mixture is stirred for a further 30 minutes at 90° C.
  15. customto fall to about 50° C.
  16. washwashed with 3 times 300 cm3 of water at about 20° C

Sources & evidence

ORD record
ord-a7a196dd2b1c4c8eab1b38259386842d
Source dataset
uspto-grants-1990_11
Patent number
US04970213

Reaction notes

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