Imidazole → HCID 10697502, compound

HRID 1736183Notes

Reaction equation

HRID 1736183 reaction equation
[F:1][C:2]1[C:3]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[C:4]([C:10]([NH:16][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[C:11]([F:15])[C:12]=1[CH2:13][OH:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6].N1C=CN=C1.[Si:35](Cl)([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36].O>ClCCl>[Si:35]([O:14][CH2:13][C:12]1[C:11]([F:15])=[C:10]([NH:16][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[C:3]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[C:2]=1[F:1])([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 10693183HCID 10693183, compound

Product 1

HCID 10697502HCID 10697502, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

213 mg (0.50 mmol) of the above ethyl 3,5-difluoro-4-hydroxymethyl-6-pivaloylamino-2-(2-tetrahydropyranyloxy)benzoate was dissolved in 5 mL of dichloromethane, 68 mg (1.0 mmol) of imidazole and 302 mg (2.00 mmol) of tert-butyldimethylsilyl chloride were added and the mixture was heated at reflux for 30 minutes. The reaction solution was cooled on ice, water was added and the mixture was extracted once with ethyl acetate. The organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1) to give 256 mg of ethyl 4-tert-butyldimethylsilyloxymethyl-3,5-difluoro-6-pivaloylamino-2-(2-tetrahydropyranyloxy)benzoate (yield: 98%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 30 minutes
  3. additionwas added
  4. extractionthe mixture was extracted once with ethyl acetate
  5. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-299282f8d2ce464f9e485d3be287f238
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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