Succinic Acid → Tafenoquine succinate

HRID 857442Notes

Reaction equation

HRID 857442 reaction equation
[CH3:1][CH:2]([NH:9][C:10]1[CH:11]=[C:12]([O:34][CH3:35])[C:13]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[C:14]2[C:19]=1[N:18]=[C:17]([O:20][CH3:21])[CH:16]=[C:15]2[CH3:22])[CH2:3][CH2:4][CH2:5][N+:6]([O-])=O.[H][H].[C:38]([OH:45])(=[O:44])[CH2:39][CH2:40][C:41]([OH:43])=[O:42]>[Pd].C(O)C>[C:38]([OH:45])(=[O:44])[CH2:39][CH2:40][C:41]([OH:43])=[O:42].[NH2:6][CH2:5][CH2:4][CH2:3][CH:2]([NH:9][C:10]1[CH:11]=[C:12]([O:34][CH3:35])[C:13]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[CH:25]=2)=[C:14]2[C:19]=1[N:18]=[C:17]([O:20][CH3:21])[CH:16]=[C:15]2[CH3:22])[CH3:1]

Participants

6

Reactant 3

HCID 1110Succinic AcidHCID 21868816HCID 21868816, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 163761Tafenoquine succinateYield 68%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of the product from example 2.2 (7.5 g, 15.2 mmol), ethanol (150 ml) and 5% Pd—C (2 g) was stirred under ca. 1 bar hydrogen for 24 hours at ambient temperature. The catalyst was filtered off and the solvent evaporated to leave a volume of ca. 25 ml. Succinic acid (2.3 g, 19.8 mmol) was added, and the mixture heated under reflux for 30 minutes. The solution was then cooled to 0–5° C., seeded with authentic target compound, and stirred for 2 hours. The crystalline product was filtered off, washed with ethanol (15 ml) and dried in vacuo at 50° C. for 24 hours to give 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-(3-trifluoromethylphenoxy)quinoline succinate as an off-white crystalline solid (6.0 g, 68%).

Workup

  1. filtrationThe catalyst was filtered off
  2. customthe solvent evaporated
  3. customto leave a volume of ca. 25 ml
  4. temperaturethe mixture heated
  5. temperatureunder reflux for 30 minutes
  6. temperatureThe solution was then cooled to 0–5° C.
  7. filtrationThe crystalline product was filtered off
  8. washwashed with ethanol (15 ml)
  9. customdried in vacuo at 50° C. for 24 hours

Sources & evidence

ORD record
ord-860c20c544a341bc80bdc688679b4a61
Source dataset
uspto-grants-2006_12
Patent number
US07145014B2

Reaction notes

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