N-Ethylaniline → Laquinimod

HRID 1039622Notes

Reaction equation

HRID 1039622 reaction equation
[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].ClP(Cl)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[OH:31][C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][C:40]=2[Cl:42])[N:35]([CH3:43])[C:34](=[O:44])[C:33]=1[C:45](O)=[O:46]>C(Cl)(Cl)Cl>[CH3:2][CH2:1][N:3]([C:45]([C:33]1[C:34](=[O:44])[N:35]([CH3:43])[C:36]2[CH:37]=[CH:38][CH:39]=[C:40]([Cl:42])[C:41]=2[C:32]=1[OH:31])=[O:46])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 7670N-EthylanilineHCID 260420Triphenylphosphine dichlorideHCID 547202275-Chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Product 1

HCID 54677946LaquinimodYield 92.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
27.5 °C

Procedure

N-Ethyl aniline (5.2 gm) was taken in chloroform (100 ml) and stirred for 10 minutes at 25-30° C. under nitrogen atmosphere. The resulting mass was followed by the addition of dichlorotriphenyl phosphorane (26.6 gm) at 25-30° C. and the reaction mixture was stirred for 15 minutes. 1,2-Dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid (10 gm) was added to the resulting mass at 25-30° C. followed by heating to reflux (40-45° C.) and then stirred for 3 hours at reflux. Chloroform was distilled out from the reaction mass under vacuum at below 55° C. The resulting residue was cooled to 25-30° C., followed by the addition of ethyl acetate (50 ml) and water (50 ml) at 25-30° C. and the resulting mixture was stirred for 30 minutes at 25-30° C. The separated solid was filtered, washed with water and then dried to yield 12.95 gm of laquinimod (HPLC purity: 99.24%).

Workup

  1. stirringthe reaction mixture was stirred for 15 minutes
  2. temperatureby heating
  3. temperatureto reflux (40-45° C.)
  4. stirringstirred for 3 hours
  5. temperatureat reflux
  6. distillationChloroform was distilled out from the reaction mass under vacuum at below 55° C
  7. temperatureThe resulting residue was cooled to 25-30° C.
  8. additionfollowed by the addition of ethyl acetate (50 ml) and water (50 ml) at 25-30° C.
  9. stirringthe resulting mixture was stirred for 30 minutes at 25-30° C
  10. filtrationThe separated solid was filtered
  11. washwashed with water
  12. customdried

Sources & evidence

ORD record
ord-07248633b2a645f0a7b1ea58d61966de
Source dataset
uspto-grants-2013_10
Patent number
US08552194B2

Reaction notes

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