Ammonium Chloride → Samidorphan

HRID 1043976Notes

Reaction equation

HRID 1043976 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@:12]34[C:13]5[C:14]6[O:23][C@H:11]3[C:10](=[O:26])[CH2:9][CH2:8][C@@:7]4([OH:27])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]([NH2:22])=[O:21])[CH2:3][CH2:2]1.[Cl-].[NH4+]>C(O)C.[Zn]>[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@@:12]34[C:13]5[C:14]([OH:23])=[C:15]([C:20]([NH2:22])=[O:21])[CH:16]=[CH:17][C:18]=5[CH2:19][C@@H:6]2[C@:7]3([OH:27])[CH2:8][CH2:9][C:10](=[O:26])[CH2:11]4)[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 10021946Samidorphan

Product 1

HCID 11667832SamidorphanYield 48%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (3.0 g, 8.15 mmol), Zinc powder (2.67 g, 40.76 mmol), and ammonium chloride (3.05 g, 57.1 mmol) in ethanol (500 mL) was heated at 90° C. for 1 hour. The reaction mixture was allowed to return to room temperature then filtered. The residual solid was washed with excess methanol (500 mL) followed by 7% ammonium hydroxide (100 mL). The combined filtrates were concentrated under reduced pressure and the residue partitioned between dichloromethane and 7% ammonium hydroxide solution. The aqueous phase was washed with further DCM and the combined organic layers dried (MgSO4). Filtration and removal of the solvent under reduced pressure giving 17-(cyclopropylmethyl)-4,14-dihydroxy-6-oxomorphinan-3-carboxamide [P4] (1.45 g, 48% yield); LC/MS (r.t. 10.7 minutes [5 to 95% B]), 371 (M+H)+.

Workup

  1. customto return to room temperature
  2. filtrationthen filtered
  3. washThe residual solid was washed with excess methanol (500 mL)
  4. concentrationThe combined filtrates were concentrated under reduced pressure
  5. customthe residue partitioned between dichloromethane and 7% ammonium hydroxide solution
  6. washThe aqueous phase was washed with further DCM
  7. dry with materialthe combined organic layers dried (MgSO4)
  8. filtrationFiltration and removal of the solvent under reduced pressure

Sources & evidence

ORD record
ord-9ee7f6592190481788fd87f399e35a76
Source dataset
uspto-grants-2013_10
Patent number
US08563572B2

Reaction notes

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