Methanol → 1-t-butoxycarbonyl-4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

HRID 1584450Notes

Reaction equation

HRID 1584450 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][CH2:21][O:22][Si](C(C)(C)C)(C)C)[C:18]3[CH:30]=[CH:31][CH:32]=[CH:33][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[F-].[NH4+]>C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][CH2:21][OH:22])[C:18]3[CH:30]=[CH:31][CH:32]=[CH:33][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 887MethanolHCID 25516Ammonium fluorideHCID 18464522HCID 18464522, compound

Product 1

HCID 184648041-t-butoxycarbonyl-4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combine 1-(t-butoxycarbonyl)-4-(1-(2-(t-butyldimethylsilyloxy)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (4.22 g, 8.88 mmol), and methanol (60 mL). Add ammonium fluoride (1.97 g, 53.3 mmol). Heat to reflux. After 2 hours, cool the reaction mixture and partition between dichloromethane (300 mL) and a saturated aqueous solution of sodium bicarbonate (200 mL). Separate the layers and extract the organic layer three times with water and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with ethyl acetate to give 1-(t-butoxycarbonyl)-4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf =0.32 (silica gel, ethyl acetate).

Workup

  1. temperatureHeat to reflux
  2. temperaturecool the reaction mixture
  3. custompartition between dichloromethane (300 mL)
  4. customSeparate the layers
  5. extractionextract the organic layer three times with water
  6. dry with materialDry the organic layer over MgSO4
  7. filtrationfilter
  8. customevaporate in vacuo
  9. customto give a residue

Sources & evidence

ORD record
ord-92d2ecba49bf411095433d2203e437ac
Source dataset
uspto-grants-1999_08
Patent number
US05932571

Reaction notes

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