Ethyl Acetate → HCID 18464522, compound

HRID 1584448Notes

Reaction equation

HRID 1584448 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Si:26]([O:33][CH2:34][CH2:35]I)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27].C(OCC)(=O)C>O1CCCC1.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:35][CH2:34][O:33][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 11129873tert-Butyl(2-iodoethoxy)dimethylsilaneHCID 184646551-t-butoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

Product 1

HCID 18464522HCID 18464522, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Combine 2-(t-butyldimethylsilyloxy)ethyl bromide (116.2 g, 486 mmol), and sodium iodide (100 g, 663 mol) in acetone (350 mL) and dimethylformamide (25 mL). Heat to reflux. After 4 hours, cool, filter, and evaporate in vacuo to give a residue. Distill the residue to give 2-(t-butyldimethylsilyloxy)ethyl iodide: bp; 60° C. at 0.5 mm Hg. Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepane (3.06 g, 9.67 mmol) and sodium hydride (0.43 g, 60% in oil, 10.64 mmol) in tetrahydrofuran (60 mL) and dimethylformamide (6 mL). After 2 hours, add 2-(t-butyldimethylsilyloxy)ethyl iodide (2.78 g, 9.67 mmol). After 20 hours, heat to reflux. After 4 hours, cool to ambient temperature and add ice to quench. Evaporate in vacuo to remove most of the tetrahydrofuran. Partition the evaporated reaction mixture between ethyl acetate (250 mL) and water (200 mL). Separate the layers and extract the organic layer with water. 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-(t-butyldimethylsilyloxy)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf =0.58 (silica gel, ethyl acetate).

Workup

  1. waitAfter 20 hours
  2. temperatureheat to reflux
  3. waitAfter 4 hours
  4. additionadd ice
  5. customto quench
  6. customEvaporate in vacuo
  7. customto remove most of the tetrahydrofuran
  8. customPartition
  9. customthe evaporated reaction mixture between ethyl acetate (250 mL) and water (200 mL)
  10. customSeparate the layers
  11. extractionextract the organic layer with water
  12. dry with materialDry the organic layer over MgSO4
  13. filtrationfilter
  14. customevaporate in vacuo
  15. customto give a residue

Sources & evidence

ORD record
ord-f38306a4bdfc43f380bb8be47ff9ec70
Source dataset
uspto-grants-1999_08
Patent number
US05932571

Reaction notes

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