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

HRID 344875Notes

Reaction equation

HRID 344875 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

Conditions

Temperature
20 °C

Procedure

Phosphoryl chloride (76.9 cc) is added in the course of 30 minutes, with stirring and at between 10° and 15° C. to a mixture of trichloromethane (800 cc) and dimethylformamide (74.35 cc), and the mixture is stirred for 1 hour at a temperature in the region of 20° C. To the solution obtained, 6,7-difluoro-3,4-dihydrocarbostyril (65.8 g) is added in the course of 10 minutes at approximately 20° C. with vigorous stirring. The suspension obtained is heated to a temperature in the region of 60° C. and maintained 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 ice (500 g) and water (500 cc) is added with vigorous stirring. The solid obtained is drained at approximately 5° C. and washed with water (3×300 cc) at 5° C. The wet product obtained and sodium acetate (60 g) are added simultaneously in the course of 1 hour to water (1.5 liters) at 90° C., so as to maintain the pH at approximately 6. The mixture is stirred for a further 30 minutes at 90° C., the temperature is allowed to fall to approximately 50° C. and the product is drained at this temperature and washed with water (3×300 cc) at approximately 20° C. 2-Chloro-6,7-difluoro-3-formyl-1,4-dihydroquinoline 70.18 g) is obtained in the form of a yellow solid, m.p. 260° C., which is used without further treatment for the subsequent steps.

Workup

  1. customTo the solution obtained
  2. customThe suspension obtained
  3. temperatureis heated to a temperature in the region of 60° C.
  4. temperaturemaintained at this temperature for 2 hours
  5. concentrationThe reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture
  6. customis obtained
  7. additionis added with vigorous stirring
  8. customThe solid obtained
  9. customis drained at approximately 5° C.
  10. washwashed with water (3×300 cc) at 5° C
  11. customThe wet product obtained
  12. temperatureso as to maintain the pH at approximately 6
  13. stirringThe mixture is stirred for a further 30 minutes at 90° C.
  14. customto fall to approximately 50° C.
  15. washwashed with water (3×300 cc) at approximately 20° C

Sources & evidence

ORD record
ord-eabb25451ea14a01b5cef04f1ddc873d
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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