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

HRID 1073585Notes

Reaction equation

HRID 1073585 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

Procedure

55.6 cm3 of phosphoryl chloride are added in the course of 30 minutes, with stirring, at between 10 and 15° C., to a mixture of 250 cm3 of trichloromethane and 54 cm3 of dimethylformamide and the mixture is stirred for 1 hour at a temperature close to 20° C. 52 g of 7-chloro-6-fluoro-3,4-dihydrocarbostyril are added progressively, with vigorous stirring, in the course of 10 minutes, at about 20° C. to the solution obtained. The suspension obtained is heated to a temperature close to 60° C. and is kept at this temperature for a further 2 hours, with stirring. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of 250 cm3 of water and 250 g of crushed ice is added, with vigorous stirring. The solid obtained is drained at about 5° C. and washed with 4 times 125 cm3 of water at 5° C. The moist product obtained and 58 g of sodium acetate are added simultaneously , in the course of 1 hour, to 500 cm3 of water at 90° C. in such a way as to maintain the pH at about 6. The mixture is stirred for a further 15 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 250 cm3 of water at about 20° C. 54.3 g of 2,7-dichloro-6-fluoro-3-formyl-1,4-dihydro quinoline 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. waitis kept at this temperature for a further 2 hours
  7. stirringwith stirring
  8. concentrationThe reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture
  9. customis obtained
  10. additionis added, with vigorous stirring
  11. customThe solid obtained
  12. customis drained at about 5° C.
  13. washwashed with 4 times 125 cm3 of water at 5° C
  14. customThe moist product obtained
  15. temperatureto maintain the pH at about 6
  16. stirringThe mixture is stirred for a further 15 minutes at 90° C.
  17. customto fall to about 50° C.
  18. washwashed with 3 times 250 cm3 of water at about 20° C

Sources & evidence

ORD record
ord-dada6ab3e61a4368804db2f48a6d04bc
Source dataset
uspto-grants-1990_11
Patent number
US04970213

Reaction notes

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