Sodium Hydroxide → Laquinimod Sodium

HRID 1804754Notes

Reaction equation

HRID 1804754 reaction equation
[CH2:1]([N:3]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:4]([C:6]1[C:7](=[O:19])[N:8]([CH3:18])[C:9]2[C:14]([C:15]=1[OH:16])=[C:13]([Cl:17])[CH:12]=[CH:11][CH:10]=2)=[O:5])[CH3:2].[OH-].[Na+:27]>C(O)C>[CH3:2][CH2:1][N:3]([C:4]([C:6]1[C:7](=[O:19])[N:8]([CH3:18])[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([Cl:17])[C:14]=2[C:15]=1[O-:16])=[O:5])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1.[Na+:27]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 54677946Laquinimod

Product 1

HCID 23697158Laquinimod SodiumYield 75.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
2.5 °C

Procedure

N-Ethyl-N-phenyl-1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide (35 gm) was suspended in ethanol (140 ml) at 20-25° C. under stirring followed by the addition of freshly prepared sodium hydroxide solution (4.13 gm of sodium hydroxide in 11 ml of water) at 20-25° C. and then stirred for 15-30 minutes at 25-30° C. The resulting solution was filtered through a hyflow super cell bed and the bed was washed with ethanol (105 ml) at 25-30° C. The resulting filtrate was seeded with pure laquinimod sodium (0.175 gm) and then stirred for 4 hours at 25-30° C. The resulting mass was cooled to 0-5° C. followed by stirring for 2 hours at the same temperature. The resulting white colored solid was filtered, washed with chilled ethanol (38 ml) and then dried under vacuum at 60-65° C. to yield 28 gm of laquinimod sodium in crystalline Form A1 (HPLC Purity: 99.9%; Bulk density: 0.333 g/ml; Tapped density: 0.476 g/ml; and Particle size distribution: d(0.9)=26.3 microns).

Workup

  1. stirringstirred for 15-30 minutes at 25-30° C
  2. filtrationThe resulting solution was filtered through a hyflow super cell bed
  3. washthe bed was washed with ethanol (105 ml) at 25-30° C
  4. stirringstirred for 4 hours at 25-30° C
  5. stirringby stirring for 2 hours at the same temperature
  6. filtrationThe resulting white colored solid was filtered
  7. washwashed with chilled ethanol (38 ml)
  8. customdried under vacuum at 60-65° C.

Sources & evidence

ORD record
ord-d118fbb9f1694295896fbb42178053a1
Source dataset
uspto-grants-2013_01
Patent number
US08354428B2

Reaction notes

Loading…