4-Methylmorpholine → 1-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidine

HRID 1682978Notes

Reaction equation

HRID 1682978 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2([CH2:16][CH2:17][OH:18])[CH2:15][CH2:14][NH:13][CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CN1CCOCC1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([O:39][CH3:40])[C:36]=1[O:37][CH3:38])[C:31](Cl)=[O:32].C(=O)=O.CC(C)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2([CH2:16][CH2:17][OH:18])[CH2:15][CH2:14][N:13]([C:31](=[O:32])[C:30]3[CH:29]=[C:28]([O:27][CH3:26])[C:36]([O:37][CH3:38])=[C:35]([O:39][CH3:40])[CH:34]=3)[CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 153920213-(3,4-Dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidineHCID 18522661Acetone cardice

Product 1

HCID 184649141-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

2-[3-(3,4-Dimethoxy-phenyl)-pyrrolidin-3-yl]-ethanol (2.27 g, 9.03 mmol) and dichloromethane (100 mL) were combined. 4-Methylmorpholine (2.28 mL, 22.6 mmol, 2.5 eq.) was added. The mixture was cooled in a ice/NaCl bath and a solution of 3,4,5-trimethoxy-benzoyl chloride (2.19 g, 9.48 mmol) in dichloromethane (30 mL) was added dropwise. After the addition was complete, the dry-ice/acetone bath was changed to an ice bath and the mixture was allowed to warm to ambient temperature and maintained overnight. The solution was extracted with 1N HCl (3×100 mL), saturated K2CO3 (3×100 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to obtain a residue. The residue was purified by chromatography on silica gel eluting with ethyl acetate/methanol (20:1) to obtain a residue. The residue was dissolved in dichloromethane (50 mL), extracted with water (2×50 mL), dried over Na2SO4, filtered, and concentrated in vacuo to obtain a residue. Heated at 110° C./0.3 Torr for 16 h to obtain the title compound: Rf =0.14 (silica gel, 20:1 ethyl acetate/methanol), mp=60°-62° C.

Workup

  1. temperatureThe mixture was cooled in a ice/NaCl bath
  2. additionAfter the addition
  3. temperaturemaintained overnight
  4. extractionThe solution was extracted with 1N HCl (3×100 mL), saturated K2CO3 (3×100 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto obtain a residue
  9. customThe residue was purified by chromatography on silica gel eluting with ethyl acetate/methanol (20:1)
  10. customto obtain a residue
  11. extractionextracted with water (2×50 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto obtain a residue
  16. temperatureHeated at 110° C./0.3 Torr for 16 h

Sources & evidence

ORD record
ord-f9c30d84075c4c219e733faa1635ae48
Source dataset
uspto-grants-1997_06
Patent number
US05635510

Reaction notes

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