Hydrochloric Acid → benzyl {2-(4-bromophenyl)-1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}carbamate

HRID 1881462Notes

Reaction equation

HRID 1881462 reaction equation
Cl.[CH2:2]([O:9][C:10]([NH:12][CH:13]([C:22]1[N:23](C(OC(C)(C)C)=O)[CH:24]=[C:25]([CH2:27][C:28]([CH3:32])([CH3:31])[CH2:29][CH3:30])[N:26]=1)[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH3:47][N:48]([CH3:53])[S:49](Cl)(=[O:51])=[O:50]>CO.C(Cl)Cl.O>[Br:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][CH:13]([NH:12][C:10](=[O:11])[O:9][CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:22]2[N:23]([S:49]([N:48]([CH3:53])[CH3:47])(=[O:51])=[O:50])[CH:24]=[C:25]([CH2:27][C:28]([CH3:31])([CH3:32])[CH2:29][CH3:30])[N:26]=2)=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 83372Dimethylsulphamoyl chlorideHCID 66705603tert-butyl 2-[1-{[(benzyloxy)carbonyl]amino}-2-(4-bromophenyl)ethyl]-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate

Product 1

HCID 86637798benzyl {2-(4-bromophenyl)-1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}carbamate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

Hydrogen chloride (4 M in 1,4-dioxane) (2 mL, 8 mmol) was added to an ambient temperature solution of tert-butyl 2-[1-{[(benzyloxy)carbonyl]amino}-2-(4-bromophenyl)ethyl]-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate (for synthesis see Example 37) (600 mg, 1.03 mmol) in methanol (4 mL). After stirring at 70° C. for 1 h, volatiles were removed in vacuo. The residue was partitioned between methanol/ethyl acetate and 10% aqueous sodium hydroxide. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Triethylamine (0.43 mL, 3.09 mmol) followed by dimethylsulfamoyl chloride (0.22 mL, 2.06 mmol) were added to an ambient temperature solution of the crude residue in methylene chloride (10 mL). After stirring at ambient temperature overnight, the reaction mixture was diluted with water and extracted with ethyl acetate and methylene chloride. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo to afford benzyl {2-(4-bromophenyl)-1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}carbamate which was used in the subsequent step without further purification.

Workup

  1. customvolatiles were removed in vacuo
  2. customThe residue was partitioned between methanol/ethyl acetate and 10% aqueous sodium hydroxide
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  5. concentrationconcentrated in vacuo
  6. stirringAfter stirring at ambient temperature overnight
  7. extractionextracted with ethyl acetate and methylene chloride
  8. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b6ad0f0ed7f044a8975b557853364d09
Source dataset
uspto-grants-2012_11
Patent number
US08318767B2

Reaction notes

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