Ammonium Chloride → HCID 22877439, compound

HRID 1740253Notes

Reaction equation

HRID 1740253 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:32])([CH3:31])[C:13]([NH:15][C@@H:16]1[CH2:22][CH2:21][C:20]2[CH:23]=[C:24]([N+:27]([O-])=O)[CH:25]=[CH:26][C:19]=2[NH:18][C:17]1=[O:30])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+]>CO.[Zn]>[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:32])([CH3:31])[C:13]([NH:15][C@@H:16]1[CH2:22][CH2:21][C:20]2[CH:23]=[C:24]([NH2:27])[CH:25]=[CH:26][C:19]=2[NH:18][C:17]1=[O:30])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 22877444HCID 22877444, compound

Product 1

HCID 22877439HCID 22877439, compoundYield 85.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

To a solution of 310 mg (0.73 mmol) 2-benzyloxycarbonylamino-2-methyl-N-[7-nitro-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide (Step B) in 20 mL of methanol was added 78 mg (1.5 mmol) of ammonium chloride followed by 669 mg (10.2 mmol) of zinc dust. The resulting mixture was heated at reflux for four hours. The solids were removed by filtration through Celite. The filter pad was washed with 30 mL of hot methanol. The filtrate was combined and the solvent was removed under vacuum. The residue was dissolved in 10 mL of 1N aqueous hydrochloric acid and the solids were filtered away. To the resulting solution was added sufficient 5N aqueous sodium hydroxide until the pH was approximately 12. The solution was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water then brine, dried over magnesium sulfate and filtered. The solvent was removed under vacuum to afford 256 mg (85%) of the product as a white solid. 1H NMR (400 MHz, CDCl3): δ 1.48 (s, 3H), 1.50 (s, 3H), 1.78 (m, 1H), 2.47 (m, 1H), 2.71 (m, 1H), 2.82 (m, 1H), 3.67 (s, 2H), 4.44 (m, 1H), 5.05 (s, 2H), 5.39 (s, 1H), 6.50 (m, 2H), 6.74 (d, 8 Hz, 1H), 7.04 (d, 7 Hz, 1H), 7.32 (m, 6H). FAB-MS: calculated for C22H26N4O4 410; found 411 (M+H, 100%).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for four hours
  3. customThe solids were removed by filtration through Celite
  4. washThe filter pad was washed with 30 mL of hot methanol
  5. customthe solvent was removed under vacuum
  6. dissolutionThe residue was dissolved in 10 mL of 1N aqueous hydrochloric acid
  7. filtrationthe solids were filtered away
  8. additionTo the resulting solution was added sufficient 5N aqueous sodium hydroxide until the pH was approximately 12
  9. extractionThe solution was extracted with ethyl acetate (3×50 mL)
  10. washThe combined organic extracts were washed with water
  11. dry with materialbrine, dried over magnesium sulfate
  12. filtrationfiltered
  13. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-834eb69d5b7c402f940d200491395a4b
Source dataset
uspto-grants-1999_10
Patent number
US05968924

Reaction notes

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