Ammonium Hydroxide → HCID 178501363, compound

HRID 1177717Notes

Reaction equation

HRID 1177717 reaction equation
C(O)(=O)C.[CH3:5][O:6][C:7](=[O:29])[C@H:8]([NH:18][C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([NH2:17])[CH:11]=1.[N:30]([O-])=O.[Na+].[OH-].[NH4+]>C(O)(=O)C.O>[CH3:5][O:6][C:7](=[O:29])[C@H:8]([NH:18][C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]2[NH:16][N:30]=[N:17][C:12]=2[CH:11]=1

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 23668193Sodium NitriteHCID 25136600HCID 25136600, compound

Product 1

HCID 178501363HCID 178501363, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

To a solution of (R)-2-benzyloxycarbonylamino-3-(3,4-diamino-phenyl)-propionic acid methyl ester mono acetate (2.68 g, 6.65 mmol) in acetic acid (30 mL) and water (40 mL), at room temperature was added a solution of sodium nitrite (0.46 g, 6.65 mmol) in water (8 mL), dropwise over several minutes. The resulting mixture was stirred at room temperature for 20 min, then cooled to 0° C., concentrated ammonium hydroxide was added to adjust pH to 11. The mixture was extracted with ethyl acetate twice in the presence of solid sodium chloride, and the organic layers were dried over sodium sulfate. After filtration, solvents were removed in vacuo and the residue was purified by chromatography on silica gel using ethyl acetate/hexanes (6:4) as eluent to afford the title compound as a tan solid (94% yield). 1H-NMR (CD3OD, 500 MHz) δ 7.75 (d, J=8.5 Hz, 1H), 7.58 (s, 1H), 7.31-7.25 (m, 5H), 7.18 (d, J=8.5 Hz, 1H), 5.39 (d, J=8.0 Hz, 1H), 5.10 (d, J=12.0 Hz, 1H), 5.05 (d, J=12.0 Hz, 1H), 4.74 (dd, j=13.5, 6.0 Hz, 1H), 3.73 (s, 3H), 3.34 (dd, J=14.0, 5.5 Hz,1H), 3.22 (dd, J=13.5, 6.0 Hz, 1H). 13CNMR (CD3OD, 125 MHz) δ 172.1, 156.0, 136.1, 128.6, 128.3, 128.1, 67.2, 55.2, 52.7, 38.5. Mass spec. 355.18 (MH)+.

Workup

  1. waitdropwise over several minutes
  2. temperaturecooled to 0° C.
  3. extractionThe mixture was extracted with ethyl acetate twice in the presence of solid sodium chloride
  4. dry with materialthe organic layers were dried over sodium sulfate
  5. filtrationAfter filtration, solvents
  6. customwere removed in vacuo
  7. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-fb0b49d288ba48e99e0d6cef7cf38cb7
Source dataset
uspto-grants-2010_11
Patent number
US07842808B2

Reaction notes

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