Ammonium Hydroxide → HCID 178501367, compound

HRID 2355978Notes

Reaction equation

HRID 2355978 reaction equation
[CH3:1][O:2][C:3]([C@H:5]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([NH2:14])=[C:9]([NH2:15])[CH:8]=1)=[O:4].[N:27]([O-])=O.[Na+].[OH-].[NH4+]>C(O)(=O)C.O>[CH3:1][O:2][C:3]([C@H:5]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]2[NH:14][N:27]=[N:15][C:9]=2[CH:8]=1)=[O:4]

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 23668193Sodium NitriteHCID 42644537HCID 42644537, compound

Product 1

HCID 178501367HCID 178501367, compoundYield 72.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent3×

Procedure

To a solution of benzyl (R)-1-(methoxycarbonyl)-2-(3,4-diamino-5-methylphenyl)ethylcarbamate (250 mg, 0.58 mmol) in acetic acid (6 mL) and water (10 mL) was added a solution of sodium nitrite (40 mg, 0.58 mmol) in water (1 mL), dropwise over several minutes at room temperature. The resulting mixture was stirred at room temperature for 30 min, then cooled to 0° C. A mixture of ammonium hydroxide and water (1:1, 15 mL) was added to adjust pH to 11. The mixture was extracted with ethyl acetate twice. The organic layers washed with brine and dried over sodium sulfate. After filtration, solvents were removed in vacuo and the residue was purified by flash column chromatography (1:1 ethyl acetate/hexanes) on silica gel to afford the title compound as a tan solid (155 mg, 72% yield). 1H-NMR (CDCl3, 300 MHz) δ 7.34 (s, 1H), 7.32-7.28 (m, 6H), 6.93 (s, 1H), 5.40 (d, J=8.1 Hz, 1H), 5.13-5.02 (m, 2H), 4.76-4.69 (m, 1H), 3.73 (s, 3H), 3.28 (dd, J=13.9, 5.5 Hz, 1H), 3.16 (dd, J=13.9, 6.2 Hz, 1H), 2.64 (s, 3H). LC/MS: tR=2.30 min, 369 (MH)+.

Workup

  1. waitdropwise over several minutes at room temperature
  2. temperaturecooled to 0° C
  3. additionwas added
  4. extractionThe mixture was extracted with ethyl acetate twice
  5. washThe organic layers washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration, solvents
  8. customwere removed in vacuo
  9. customthe residue was purified by flash column chromatography (1:1 ethyl acetate/hexanes) on silica gel

Sources & evidence

ORD record
ord-cd8676b980e2455ea7eb6d2b70deb589
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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