Tetrahydrofuran → Ammonia

HRID 2230540Notes

Reaction equation

HRID 2230540 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.[CH:54]([S:56]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)(=[O:58])=[O:57])=[CH2:55]>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]([CH2:55][CH2:54][S:56]([C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=4)(=[O:57])=[O:58])[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 8028TetrahydrofuranHCID 79664Phenyl vinyl sulfone3×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 0.5%HCID 18464482HCID 18464482, 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)(0.63 g, 1.07 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. using a dry-ice /acetone bath. Add dropwise a solution of sec-butyllithium (1.23 mL, 1.3 M, 1.61 mmol). When the addition of sec-butyllithium is complete, add a solution phenyl vinyl sulfone (0.36 g, 2.14 mmol). Heat the reaction mixture to reflux. After 12 hours, cool, add phenyl vinyl sulfone (0.36 g, 2.14 mmol) and again heat the reaction mixture to reflux. After 3 hours, cool, add phenyl vinyl sulfone (0.36 g, 2.14 mmol) and again heat the reaction mixture to reflux. After 2.5 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/5% methanol/dichloromethane to give the title compound.

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureto reflux
  3. temperaturecool
  4. temperatureagain heat the reaction mixture
  5. temperatureto reflux
  6. waitAfter 3 hours
  7. temperaturecool
  8. temperatureagain heat the reaction mixture
  9. temperatureto reflux
  10. waitAfter 2.5 hours
  11. temperaturecool
  12. customseparate the layers
  13. extractionextract the aqueous layer twice with ethyl acetate
  14. dry with materialdry over Na2SO4
  15. filtrationfilter
  16. customevaporate in vacuo
  17. customto give a residue

Sources & evidence

ORD record
ord-58354d0972014d5189805e654a56aba2
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

Loading…