Sodium hydride → 1-(t-butoxycarbonyl)-4-(fur-2-ylmethyl-1H-benzimidazol-2-yl)[1,4]diazepane

HRID 1584476Notes

Reaction equation

HRID 1584476 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+].Cl[CH2:27][C:28]1[O:29][CH:30]=[CH:31][CH:32]=1.[Cl-].[NH4+]>O1CCCC1.CN(C)C=O.C(OCC)(=O)C.CCCCCC>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:27][C:28]3[O:29][CH:30]=[CH:31][CH:32]=3)[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

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2195202-(Chloromethyl)furanHCID 184646551-t-butoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

Product 1

HCID 184648751-(t-butoxycarbonyl)-4-(fur-2-ylmethyl-1H-benzimidazol-2-yl)[1,4]diazepane

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Combine 1-t-butoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane (1.70 g, 5.4 mmol) in tetrahydrofuran (45 mL) and dimethylformamide (5 mL). Cool in an ice bath. Add sodium hydride (0.32 g, 60% in oil, 8.1 mmol) portionwise. After 15 minutes, warm to ambient temperature. After about 30 minutes, when the gas evolution ceases, add 2-(chloromethyl)furan (0.94 g, 8.1 mmol). After 18 hours, cool in an ice bath, add ice and then a saturated aqueous solution of ammonium chloride. Evaporate the reaction mixture to remove most of the tetrahydrofuran, dilute with ethyl acetate and extract with a saturate aqueous solution of sodium bicarbonate and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 50% ethyl acetate/hexane to give 1-t-butoxycarbonyl-4-(1-(fur-2-ylmethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf =0.47 (silica gel, ethyl acetate).

Workup

  1. temperatureCool in an ice bath
  2. waitAfter about 30 minutes
  3. waitAfter 18 hours
  4. temperaturecool in an ice bath
  5. additionadd ice
  6. customEvaporate the reaction mixture
  7. customto remove most of the tetrahydrofuran
  8. additiondilute with ethyl acetate
  9. extractionextract with a saturate aqueous solution of sodium bicarbonate
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. customevaporate in vacuo
  13. customto give a residue

Sources & evidence

ORD record
ord-ca6b006ac52646feb3253b14e656ad2b
Source dataset
uspto-grants-1999_08
Patent number
US05932571

Reaction notes

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