Imidazole → Benzyl (4-{[tert-butyl(dimethyl)silyl]oxy}-2-{[methoxy(methyl)amino]carbonyl}phenyl)carbamate

HRID 1986426Notes

Reaction equation

HRID 1986426 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:13]=1[C:14]([OH:16])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:23][NH:24][O:25][CH3:26].C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.[Si:46](Cl)([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47].N1C=CN=C1>CN(C)C=O.O>[Si:46]([O:21][C:18]1[CH:19]=[CH:20][C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:13]([C:14]([N:24]([O:25][CH3:26])[CH3:23])=[O:16])[CH:17]=1)([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47]

Participants

9

Reactant 6

HCID 795ImidazoleHCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 183153542-(((Benzyloxy)carbonyl)amino)-5-hydroxybenzoic acid

Product 1

HCID 86605626Benzyl (4-{[tert-butyl(dimethyl)silyl]oxy}-2-{[methoxy(methyl)amino]carbonyl}phenyl)carbamateYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-{[(benzyloxy)carbonyl]amino}-5-hydroxybenzoic acid (92 g, 0.32 mol) and N,O-dimethylhydroxyamine hydrochloride (38 g, 0.38 mol) in N,N-dimethylformamide (500 ml) was added triethylamine (53 ml, 0.40 mol), and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (73 g, 0.38 mol), and the mixture was stirred at room temperature for 6 hrs. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (500 ml), and tert-butyl(dimethyl)silyl chloride (48 g, 0.32 mol) and imidazole (21 g, 0.32 mol) were added. The mixture was stirred at room temperature for 6 hrs., poured into water and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give benzyl (4-{[tert-butyl(dimethyl)silyl]oxy}-2-{[methoxy(methyl)amino]carbonyl}phenyl)carbamate (91 g, yield 64%).

Workup

  1. stirringthe mixture was stirred at room temperature for 6 hrs
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in N,N-dimethylformamide (500 ml)
  7. stirringThe mixture was stirred at room temperature for 6 hrs
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated
  12. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e32406a4e7dd4e01b865e45bda3c2247
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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