Benzyloxyamine hydrochloride → HCID 18771463, compound

HRID 1387631Notes

Reaction equation

HRID 1387631 reaction equation
Cl.[CH2:2]([O:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[Al](C)C.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24]([C:33]3[CH:43]=[CH:42][C:36]([C:37](OCC)=[O:38])=[CH:35][CH:34]=3)[NH:25][C:26]=2[C:27]2[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=2)=[CH:18][CH:17]=1.CO.C(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH2:2]([O:9][NH:10][C:37](=[O:38])[C:36]1[CH:42]=[CH:43][C:33]([C:24]2[NH:25][C:26]([C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)=[C:22]([C:19]3[CH:18]=[CH:17][C:16]([F:15])=[CH:21][CH:20]=3)[N:23]=2)=[CH:34][CH:35]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 102312Benzyloxyamine hydrochlorideHCID 10134800HCID 10134800, compoundHCID 16682925TrimethylaluminumHCID 21584188Chloroform methanol

Product 1

HCID 18771463HCID 18771463, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred suspension of O-benzyl-hydroxylamine hydrochloride (1.2 g, 7.8 mmol) in toluene (20 mL) at 0° C. was added trimethylaluminum (2.0 M in toluene, 3.9 mL, 7.8 mmol). The reaction mixture was warmed to rt and stirring was continued at this temperature for 1 h. Ethyl 4-[4-(4-fluorophenyl)-5-(4-pyridyl)-1H-imidazol-2-yl]benzoate (1.0 g, 2.6 mmol) [See Ex. 14 above] was added and the reaction mixture was heated at reflux for 3 h. After cooling, the reaction was poured into 10% MeOH/CHCl3 containing silica gel. The solids were removed by filtration and washed with 10% MeOH/CHCl3. The combined washings were evaporated and the residue was purified by flash chromatography eluting with a solvent gradient of 1-10% MeOH/CHCl3. Trituration with ether afforded the title compound as a white solid (0.25 g, 21%): 1H NMR (CDCl3/MeOH-d4): d 8.16 (d, 2H); 7.77 (d, 2H); 7.53 (d, 2H); 7.23 (m, 5H); 7.10 (m, 4H); 6.88 (t, 2H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 3 h
  3. temperatureAfter cooling
  4. additioncontaining silica gel
  5. customThe solids were removed by filtration
  6. washwashed with 10% MeOH/CHCl3
  7. customThe combined washings were evaporated
  8. customthe residue was purified by flash chromatography
  9. washeluting with a solvent gradient of 1-10% MeOH/CHCl3

Sources & evidence

ORD record
ord-f918645f7614422eb5b99ba539a87618
Source dataset
uspto-grants-2001_07
Patent number
US06268370B1

Reaction notes

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