Bromoacetonitrile → HCID 18464492, compound

HRID 637082Notes

Reaction equation

HRID 637082 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][OH:22])[C:18]3[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:30][C:31]#[N:32].[Cl-].[NH4+]>C(OCC)(=O)C.O.CN(C)C=O.O1CCCC1>[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][CH2:30][C:31]#[N:32])[C:18]3[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 184648041-t-butoxycarbonyl-4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

Product 1

HCID 18464492HCID 18464492, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 1-(t-butoxycarbonyl)-4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (1.7 g, 4.7 mmol), tetrahydrofuran (70 mL), and dimethylformamide (8 mL). Cool in an ice bath. Add with stirring, sodium hydride (0.28 9, 60% in oil, 7.0 mmol). After 3 hours, warm to ambient temperature. After 30 minutes, again cool in an ice bath and add bromoacetonitrile (1.12 g, 9.36 mmol). Warm to ambient temperature. After 18 hours, again cool in an ice bath and add a saturated aqueous solution of ammonium chloride (5 mL) and then water (5 mL). Concentrate the reaction mixture in vacuo to remove most to the tetrahydrofuran and dilute with dichloromethane (150 mL). Extract three times with water, dry the organic layer over Na2SO4, 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-cyanomethyloxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf=0.38 (silica gel, ethyl acetate).

Workup

  1. temperatureCool in an ice bath
  2. additionAdd
  3. waitAfter 30 minutes
  4. temperatureagain cool in an ice bath
  5. temperatureWarm to ambient temperature
  6. waitAfter 18 hours
  7. temperatureagain cool in an ice bath
  8. concentrationConcentrate the reaction mixture in vacuo
  9. customto remove most to the tetrahydrofuran
  10. additiondilute with dichloromethane (150 mL)
  11. extractionExtract three times with water
  12. dry with materialdry the organic layer over Na2SO4
  13. filtrationfilter
  14. customevaporate in vacuo
  15. customto give a residue

Sources & evidence

ORD record
ord-9e3286d1560b46b696168f48721dbc7a
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

Loading…