Methanol → 1-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

HRID 637087Notes

Reaction equation

HRID 637087 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].Cl[C:14]1[NH:15][C:16]2[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=2[N:18]=1.CO.C(=O)(O)[O-].[Na+]>CO.ClCCl>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][CH2:10][N:9]([C:14]2[NH:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[N:15]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 785722-ChlorobenzimidazoleHCID 516892Sodium BicarbonateHCID 15289249Ethyl 1,4-diazepane-1-carboxylate

Product 1

HCID 184650911-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
130 °C

Procedure

Combine 1-ethoxycarbonyl[1,4]diazepane (18.0 g, 104 mmol) and 2-chlorobenzimidazole (7.93 g, 52 mmol). Heat to 130° C. After 4 hours, cool to ambient temperature and add hot methanol to dissolve the reaction mixture. Add a saturated aqueous solution of sodium bicarbonate (150 mL) and concentrate in vacuo to remove most of the methanol. Combine the aqueous reaction mixture and 95/5 diethyl ether/ethyl acetate. Separate the aqueous layer and extract three times with dichloromethane. Combine the dichloromethane layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Triturate the residue with ethyl acetate (100 mL) to give a solid. Chromatograph on silica gel eluting with 10% methanol/dichloromethane/0.1% concentrated aqueous ammonia to give a residue. Triturate that residue with 9/1 diethyl ether/ethyl acetate to give a solid. Collect solid by filtration and dry in vacuo to give 1-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane: mp; 161-162° C.

Workup

  1. temperaturecool to ambient temperature
  2. dissolutionto dissolve the reaction mixture
  3. concentrationconcentrate in vacuo
  4. customto remove most of the methanol
  5. customSeparate the aqueous layer
  6. extractionextract three times with dichloromethane
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give a residue
  11. customTriturate the residue with ethyl acetate (100 mL)
  12. customto give a solid
  13. customTriturate that residue with 9/1 diethyl ether/ethyl acetate
  14. customto give a solid
  15. customCollect solid
  16. filtrationby filtration
  17. customdry in vacuo

Sources & evidence

ORD record
ord-949e36073550444792b4f9ba01009380
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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