Rac-7-{[2-(tert-butyl-dimethyl-silanyl)-1-dimethylsulfamoyl-1h-imidazol-4-yl]-hydroxy-methyl}-5-methyl-benzofuran-2-carboxylic acid ethyl ester → HCID 178468500, compound

HRID 1694795Notes

Reaction equation

HRID 1694795 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[C:14]([CH:15]([C:17]3[N:18]=[C:19]([Si](C(C)(C)C)(C)C)[N:20](S(=O)(=O)N(C)C)[CH:21]=3)O)=[CH:13][C:12]([CH3:35])=[CH:11][C:9]=2[CH:10]=1)=[O:5])[CH3:2]>CCO.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[O:7][C:8]2[C:14]([CH2:15][C:17]3[N:18]=[CH:19][NH:20][CH:21]=3)=[CH:13][C:12]([CH3:35])=[CH:11][C:9]=2[CH:10]=1)=[O:5])[CH3:2]

Participants

4

Reactant 1

HCID 58951952Rac-7-{[2-(tert-butyl-dimethyl-silanyl)-1-dimethylsulfamoyl-1h-imidazol-4-yl]-hydroxy-methyl}-5-methyl-benzofuran-2-carboxylic acid ethyl ester

Product 1

HCID 178468500HCID 178468500, compoundYield 3.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of rac-7-{[2-(tert-butyl-dimethyl-silanyl)-1-dimethylsulfamoyl-1H-imidazol-4-yl]-hydroxy-methyl}-5-methyl-benzofuran-2-carboxylic acid ethyl ester (470 mg; example 52.b) in EtOH (16 ml) was treated with 10% Pd/C (117 mg) and hydrogenated for 48 hrs at 100 bar and 100° C. The reaction mixture was cooled to r.t., filtrated and concentrated. The residue was dissolved in EtOH (5 ml) and treated with 3N HCl (5 ml). The solution was heated to 100° C. for 3 hrs, then concentrated. The residue was taken up in water. The solution was made basic by the addition of K2CO3 and extracted with CH2Cl2/MeOH 4:1. The organics were dried over MgSO4, filtrated and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1) to give 7-(1H-imidazol-4-ylmethyl)-5-methyl-benzofuran-2-carboxylic acid ethyl ester (10 mg) as amorphous off-white solid. MS (ISP): 285.1 ((M+H)+.).

Workup

  1. filtrationfiltrated
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in EtOH (5 ml)
  4. additiontreated with 3N HCl (5 ml)
  5. temperatureThe solution was heated to 100° C. for 3 hrs
  6. concentrationconcentrated
  7. additionThe solution was made basic by the addition of K2CO3
  8. extractionextracted with CH2Cl2/MeOH 4:1
  9. dry with materialThe organics were dried over MgSO4
  10. filtrationfiltrated
  11. concentrationconcentrated
  12. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-8e36e4fa3906410fa2126226a7371355
Source dataset
uspto-grants-2012_04
Patent number
US08158668B2

Reaction notes

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