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

HRID 2230677Notes

Reaction equation

HRID 2230677 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].O1CCCC1.[H-].[Na+].Cl[CH2:32][C:33]1[O:34][CH:35]=[CH:36][CH:37]=1>C(OCC)(=O)C.CCCCCC.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]([CH2:32][C:33]3[O:34][CH:35]=[CH:36][CH:37]=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

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 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 2

HCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepane (1.7 g, 5.37 mmol), tetrahydrofuran (45 mL), and dimethylformamide (5 mL). Cool in an ice-bath. Add sodium hydride (0.32 g, 60%n in oil, 8.06 mmol). After 15 minutes, warm to ambient temperature. When gas evolution ceases add 2-(chloromethyl)furan (0.94 g, 8.06 mmol). After 18 hours, cool the reaction mixture, quench by the addition of a saturated aqueous ammonium chloride solution. Evaporate to remove most of the tetrahydrofuran, dilute with ethyl acetate, and extract with water, a saturated aqueous sodium bicarbonate solution, 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 50% ethyl acetate/hexane to give 1-(t-butoxycarbonyl)-4-(fur-2-ylmethyl-1H-benzimidazol-2-yl)[1,4]diazepane: Rf=0.47 (silica gel, ethyl acetate) Elemental Analysis Calculated for C22H28N4O3: C, 66.66; H, 7.17; N, 14.04. Found C, 66.65; H, 7.12; N, 14.13.

Workup

  1. temperatureCool in an ice-bath
  2. waitAfter 18 hours
  3. temperaturecool the reaction mixture
  4. customquench by the addition of a saturated aqueous ammonium chloride solution
  5. customEvaporate
  6. customto remove most of the tetrahydrofuran
  7. additiondilute with ethyl acetate
  8. extractionextract with water
  9. dry with materialDry the organic layer over MgSO4
  10. filtrationfilter
  11. customevaporate in vacuo
  12. customto give a residue

Sources & evidence

ORD record
ord-92e67d8d323342329432b3fc3e54f5e9
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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