Ammonia → Orvepitant maleate

HRID 1875432Notes

Reaction equation

HRID 1875432 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[N:14]([C:15]([N:17]([C@@H:19]([C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[CH3:20])[CH3:18])=[O:16])[CH2:13][CH2:12][C@H:11]([N:35]2[CH2:40][C@@H:39]3[CH2:41][CH2:42][C:43](=[O:44])[N:38]3[CH2:37][CH2:36]2)[CH2:10]1.Cl.[OH2:46].N.[C:48]([O:51]CC)(=[O:50])[CH3:49]>>[CH3:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[N:14]([C:15]([N:17]([C@@H:19]([C:21]2[CH:22]=[C:23]([C:31]([F:32])([F:33])[F:34])[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=2)[CH3:20])[CH3:18])=[O:16])[CH2:13][CH2:12][C@H:11]([N:35]2[CH2:40][C@@H:39]3[CH2:41][CH2:42][C:43](=[O:44])[N:38]3[CH2:37][CH2:36]2)[CH2:10]1.[CH:49](/[C:48]([OH:51])=[O:50])=[CH:42]/[C:43]([OH:44])=[O:46]

Participants

5

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 8857Ethyl AcetateHCID 71587763Orvepitant hydrochloride

Product 1

HCID 44225656Orvepitant maleate

Procedure

Orvepitant Hydrochloride (1.00 G) Was Suspended In Ethyl Acetate (20 Ml) And Water (10 ml) and 25% w/w ammonia (10 ml) were added. The aqueous layer was separated and the organic layer was washed with 10% w/w sodium chloride solution (2×10 ml). The organic solution was separated, evaporated to dryness and isopropanol (20 ml) was added. The solution was evaporated to dryness. The material was diluted with isopropanol (6 ml) and a solution of maleic acid (0.174 g) in isopropanol (2.0 ml) was added. Iso-octane (a total of 8 ml) was added and the solution was stirred overnight. The solution was evaporated to an oil. Tert-butyl methyl ether (10 ml) was added and the solution was evaporated to dryness. Repeat the addition of tert-butyl methyl ether and evaporation a total of 4 times. On final evaporation, a foam forms that solidifies to give the title compound.

Workup

  1. customThe aqueous layer was separated
  2. washthe organic layer was washed with 10% w/w sodium chloride solution (2×10 ml)
  3. customThe organic solution was separated
  4. customevaporated to dryness and isopropanol (20 ml)
  5. additionwas added
  6. customThe solution was evaporated to dryness
  7. additionThe material was diluted with isopropanol (6 ml)
  8. additiona solution of maleic acid (0.174 g) in isopropanol (2.0 ml) was added
  9. additionIso-octane (a total of 8 ml) was added
  10. customThe solution was evaporated to an oil
  11. additionTert-butyl methyl ether (10 ml) was added
  12. customthe solution was evaporated to dryness
  13. additionRepeat the addition of tert-butyl methyl ether and evaporation a total of 4 times
  14. customOn final evaporation

Sources & evidence

ORD record
ord-41049acb2be14021bafe0296fe88bf0f
Source dataset
uspto-grants-2012_11
Patent number
US08309553B2

Reaction notes

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