Water → Ammonia

HRID 637061Notes

Reaction equation

HRID 637061 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].C([Li])(CC)C.[CH:49]([S:51]([CH2:54][CH3:55])(=[O:53])=[O:52])=[CH2:50].O>O1CCCC1.CO.ClCCl>[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]([CH2:50][CH2:49][S:51]([CH2:54][CH3:55])(=[O:53])=[O:52])[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 962WaterHCID 74680(Ethylsulfonyl)ethene2×HCID 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 0.2%HCID 184648241-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-ethylsulfonylethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 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) (0.6 g, 1.0 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. using a dry-ice/acetone bath. Add dropwise a solution of sec-butyllithium (1.26 mL, 1.3 M, 1.64 mmol). When the addition of sec-butyllithium is complete, add a solution ethyl vinyl sulfone (0.37 g, 3.08 mmol) in tetrahydrofuran (2 mL). Heat the reaction mixture to reflux and seal with a rubber septum. After 18 hours, cool, add ethyl vinyl sulfone (0.37 g, 3.08 mmol) and again heat the reaction mixture to reflux. After 6 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 0.2% concentrated aqueous ammonia solution/5% methanol/dichloromethane to give the title compound.

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureto reflux
  3. customseal with a rubber septum
  4. temperaturecool
  5. temperatureagain heat the reaction mixture
  6. temperatureto reflux
  7. waitAfter 6 hours
  8. temperaturecool
  9. customseparate the layers
  10. extractionextract the aqueous layer twice with ethyl acetate
  11. dry with materialdry over Na2SO4
  12. filtrationfilter
  13. customevaporate in vacuo
  14. customto give a residue

Sources & evidence

ORD record
ord-1bb531182d374c159fa7f38ec11e95b3
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

Loading…