Hydrochloric Acid → Atrasentan Hydrochloride

HRID 496768Notes

Reaction equation

HRID 496768 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@H:13]([C:14]([OH:16])=[O:15])[C@@H:12]([C:17]3[CH:25]=[CH:24][C:20]4[O:21][CH2:22][O:23][C:19]=4[CH:18]=3)[CH2:11][N:10]2[CH2:26][C:27]([N:29]([CH2:34][CH2:35][CH2:36][CH3:37])[CH2:30][CH2:31][CH2:32][CH3:33])=[O:28])=[CH:5][CH:4]=1.[ClH:38].C(O)C>C(OCC)(=O)C>[ClH:38].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[C@H:13]([C:14]([OH:16])=[O:15])[C@@H:12]([C:17]3[CH:25]=[CH:24][C:20]4[O:21][CH2:22][O:23][C:19]=4[CH:18]=3)[CH2:11][N:10]2[CH2:26][C:27]([N:29]([CH2:30][CH2:31][CH2:32][CH3:33])[CH2:34][CH2:35][CH2:36][CH3:37])=[O:28])=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 159594rel-(2R,3R,4S)-4-(1,3-Benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-3-pyrrolidinecarboxylic acid

Product 1

HCID 159595Atrasentan HydrochlorideYield 90%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the compound of Example 501H in ethyl acetate at room temperature in a mechanically stirred vessel equipped with a thermocouple, was added 39.4 mL of 1 N HCl in ethanol (0.0394 mol) The resultant solution was filtered to remove foreign matter, concentrated in vacuo, and chased with ethyl acetate (400 mL). The solution was seeded repeatedly, as the solvent was removed, until crystallization was initiated. The mixture was concentrated to a volume of 100 mL, and the product was filtered and washed with ethyl acetate (25 mL). The resultant white solid was dried in a vacuum oven under a nitrogen purge at 50° C. to afford 17.6 g (90%) of the title compound.

Workup

  1. filtrationwas filtered
  2. customto remove foreign matter
  3. concentrationconcentrated in vacuo
  4. customwas removed, until crystallization
  5. concentrationThe mixture was concentrated to a volume of 100 mL
  6. filtrationthe product was filtered
  7. washwashed with ethyl acetate (25 mL)
  8. customThe resultant white solid was dried in a vacuum oven under a nitrogen
  9. custompurge at 50° C.

Sources & evidence

ORD record
ord-98b2140fe605438b82bb355f0a45f7b1
Source dataset
uspto-grants-2005_09
Patent number
US06946481B1

Reaction notes

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