Acrylonitrile → Ammonia

HRID 637058Notes

Reaction equation

HRID 637058 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([O:42][CH3:43])[C:39]=1[O:40][CH3:41])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]3[NH:32][C:31]4[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=4[N:29]=3)[CH2:23][CH2:22]2)([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9]1)=[O:7].O1CCCC1.C([Li])(CC)C.[C:54](#[N:57])[CH:55]=[CH2:56]>CO.ClCCl.O>[NH3:8].[CH3:43][O:42][C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:39]=1[O:40][CH3:41])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]3[N:29]([CH2:56][CH2:55][C:54]#[N:57])[C:30]4[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=4[N:32]=3)[CH2:23][CH2:22]2)([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 7855Acrylonitrile2×HCID 8028TetrahydrofuranHCID 184644781-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidineHCID 178418400CID 536281002×

Product 2

HCID 222AmmoniaYield 0.5%HCID 18464806HCID 18464806, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
-78 °C

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) (0.05 g, 0.09 mmol) and tetrahydrofuran (4 mL). Cool to −78° C. using a dry-ice/acetone bath. Add dropwise a solution of sec-butyllithium (0.08 mL, 1.3 M, 0.10 mmol). When the addition of sec-butyllithium is complete, warm the reaction mixture to ambient temperature. Add acrylonitrile (0.005 g, 0.10 mmol) and heat the reaction mixture to reflux. After 12 hours, cool, add acrylonitrile (0.01 g, 0.20 mmol), and heat the reaction mixture to reflux. After 12 hours, cool, add water, separate the layers and extract the aqueous layer twice with ethyl acetate. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 0.5% concentrated aqueous ammonia solution/3% methanol/dichloromethane to give the title compound: Rf=0.47 (silica gel,0.5% concentrated aqueous ammonia solution/3% methanol/dichloromethane).

Workup

  1. temperaturewarm the reaction mixture to ambient temperature
  2. temperatureto reflux
  3. temperaturecool
  4. temperatureheat the reaction mixture
  5. temperatureto reflux
  6. waitAfter 12 hours
  7. temperaturecool
  8. customseparate the layers
  9. extractionextract the aqueous layer twice with ethyl acetate
  10. dry with materialdry over Na2SO4
  11. filtrationfilter
  12. customevaporate in vacuo
  13. customto give a residue

Sources & evidence

ORD record
ord-e018ea6af853482a9bba0eadfd259717
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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