Dichloromethane → Laquinimod

HRID 1039620Notes

Reaction equation

HRID 1039620 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Cl:12])[N:5]([CH3:13])[C:4](=[O:14])[C:3]=1[C:15]([OH:17])=O.C(Cl)Cl.[CH2:21]([NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH3:22].S(Cl)(Cl)=O>C(N(CC)CC)C>[CH3:22][CH2:21][N:23]([C:15]([C:3]1[C:4](=[O:14])[N:5]([CH3:13])[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([Cl:12])[C:11]=2[C:2]=1[OH:1])=[O:17])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 7670N-EthylanilineHCID 24386Thionyl ChlorideHCID 547202275-Chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Product 1

HCID 54677946LaquinimodYield 55.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
7.5 °C

Procedure

The mixture of 1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid (1 gm) and methylene chloride (20 ml) was cooled to 5-10° C. under nitrogen atmosphere. Triethylamine (1.15 gm) was added to the resulting mass at 5-10° C. to form a clear solution. The solution was followed by addition of N-ethyl aniline (0.45 gm) in one portion at 5-10° C. and then thionyl chloride (0.48 gm) was added at 5-10° C. The resulting mixture was stirred for 4 hours followed by evaporation of methylene chloride under vacuum. The resulting residue was dissolved in ethyl acetate (100 ml) followed by washings with 5% sodium hydroxide solution (30 ml) at 25-30° C. The resulting aqueous layer was cooled to 10-15° C. and pH was adjusted to 2 by using 18% aqueous hydrochloric acid solution (20 ml). The resulting mass was stirred for 2 hours at 15-20° C. The resulting white colored solid was filtered and dried at 55-60° C. to yield 0.73 gm of laquinimod (HPLC Purity: 84.31%).

Workup

  1. customto form a clear solution
  2. customfollowed by evaporation of methylene chloride under vacuum
  3. dissolutionThe resulting residue was dissolved in ethyl acetate (100 ml)
  4. washfollowed by washings with 5% sodium hydroxide solution (30 ml) at 25-30° C
  5. temperatureThe resulting aqueous layer was cooled to 10-15° C.
  6. stirringThe resulting mass was stirred for 2 hours at 15-20° C
  7. filtrationThe resulting white colored solid was filtered
  8. customdried at 55-60° C.

Sources & evidence

ORD record
ord-dbd807ac15c74c8c93a4df631b693215
Source dataset
uspto-grants-2013_10
Patent number
US08552194B2

Reaction notes

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