Chloroform → 2,7-Dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline

HRID 344850Notes

Reaction equation

HRID 344850 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6]C(Cl)Cl.[Cl:10][C:11]1[CH:20]=[C:19]2[C:14]([CH2:15][CH2:16][C:17](=O)[NH:18]2)=[CH:13][C:12]=1[F:22].[C:23]([O-:26])(=O)C.[Na+]>O.CN(C)C=O>[Cl:6][C:17]1[NH:18][C:19]2[C:14]([CH2:15][C:16]=1[CH:23]=[O:26])=[CH:13][C:12]([F:22])=[C:11]([Cl:10])[CH:20]=2

Participants

7

Reactant 4

HCID 6212ChloroformHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 147005447-Chloro-6-fluoro-3,4-dihydrocarbostyril

Product 1

HCID 147005452,7-Dichloro-6-fluoro-3-formyl-1,4-dihydroquinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

Phosphoryl chloride (55.6 cc) is added in the course of 30 minutes, with stirring at between 10° and 15° C. to a mixture of trichloromethane (250 cc) and dimethylformamide (54 cc) and the mixture is stirred for 1 hour at a temperature in the region of 20° C. To the solution obtained, 7-chloro-6-fluoro-3,4-dihydrocarbostyril (52 g) is added gradually 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 kept stirring for a further 2 hours at this temperature. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of water (250 cc) and crushed ice (250 g) is added with vigorous stirring. The solid obtained is drained at approximately 5° C. and washed with water (4×125 cc) at 5° C. The wet product obtained and sodium acetate (58 g) are added simultaneously in the course of 1 hour to water (500 cc) at 90° C., so as to maintain the pH at approximately 6. The mixture is stirred for a further 15 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 (3×250 cc) at approximately 20° C. 2,7-Dichloro-6-fluoro-3-formyl1,4-dihydroquinoline (54.3 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. stirringkept stirring for a further 2 hours at this temperature
  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 (4×125 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 15 minutes at 90° C.
  14. customto fall to approximately 50° C.
  15. washwashed with water (3×250 cc) at approximately 20° C

Sources & evidence

ORD record
ord-651b647a34d14bdcaba36fa4c7b46aed
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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