Imidazole → HCID 86654777, compound

HRID 2363121Notes

Reaction equation

HRID 2363121 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6].N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>C(Cl)Cl.CCOC(C)=O>[C:26]([Si:23]([CH3:25])([CH3:24])[O:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6])([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86654778HCID 86654778, compound

Product 1

HCID 86654777HCID 86654777, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice-cold suspension of 3-hydroxy-5-trifluoromethyl-benzoic acid (1.0 mg, 4.85 mmol) and N,O-dimethylhydroxylamine hydrochloride (520 mg, 5.33 mmol) in CH2Cl2 (20 mL) was added N-methylmorpholine (586 μl, 5.33 mmol). The mixture was stirred for 5 minutes, to which were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.05 g, 5.33 mmol). The mixture was stirred for 3 hours at room temperature, and then diluted with EtOAc. The organic layer was washed with 1N HCl, water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The product was vacuum-dried to give the 3-hydroxy-N-methoxy-N-methyl-5-trifluoromethyl-benzamide. To a suspension of 3-hydroxy-N-methoxy-N-methyl-5-trifluoromethyl-benzamide (13.7 g, 44.8 mmol) and imidazole (495 mg, 7.27 mmol) in CH2Cl2 (20 mL) was added portionwise tert-butyldimethylsilyl chloride (877 mg, 5.82 mmol) at 0° C. The mixture was stirred for 3 hours at room temperature, and then diluted with EtOAc. The organic layer was washed with 1N HCl, water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography to give 3-(tert-butyl-dimethyl-silanyloxy)-N-methoxy-N-methyl-5-trifluoromethyl-benzamide (1.71 g, 97%).

Workup

  1. washThe organic layer was washed with 1N HCl, water and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by column chromatography

Sources & evidence

ORD record
ord-cc9d43330dde4c499370dc8b21492730
Source dataset
uspto-grants-2014_04
Patent number
US08691855B2

Reaction notes

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