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

HRID 323187Notes

Reaction equation

HRID 323187 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].ClCCl.CO>ClCCl.C(OCC)(=O)C.CO>[CH3:40][O:39][C:35]1[CH:34]=[C:30]([CH:29]=[C:28]([O:27][CH3:26])[C:36]=1[O:37][CH3:38])[C:31]([N:13]1[CH2:14][CH2:15][C:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)([CH2:16][CH2:17][OH:18])[CH2:12]1)=[O:32]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 153920213-(3,4-Dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidineHCID 21226129Dichloromethane methanol

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 21584119Ethylacetate methanolSolvent2×

Conditions

Temperature
-5 °C

Procedure

Combine 3-(3,4-dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidine (2.27 g, 9.03 mmol) and N-methylmorpholine (2.48 mL, 22.6 mmol) in anhydrous dichloromethane (100 mL). Cool the reaction mixture to −5° C. with an salt-ice bath. Slowly, add 3,4,5-trimethoxybenzoyl chloride (2.2 g, 9.5 mmol) as a solution in dichloromethane (30 mL). Warm to ambient temperature. After 18 hours, extract the reaction mixture with a saturated solution of potassium carbonate. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 95% dichloromethane/methanol to obtain a residue. Combine the residue and dichloromethane (100 mL), and extract 3 times with 1M hydrochloric acid solution and saturated solution of potassium carbonate. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 20/1 ethyl acetate/methanol to obtain an oil: Rf=0.14 (silica gel, 20/1 ethyl acetate/methanol). Dry in vacuo at 110° C. to obtain the title compound as a glass: mp; 60-62° C. Elemental Analysis calculated for C24H31NO7: C 64.70; H 7.01; N 3.14; Found C 64.40; H 7.21; N 2.85.

Workup

  1. temperatureWarm to ambient temperature
  2. extractionextract the reaction mixture with a saturated solution of potassium carbonate
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customto obtain a residue
  7. extractionextract 3 times with 1M hydrochloric acid solution and saturated solution of potassium carbonate
  8. dry with materialDry the organic layer over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customto obtain a residue
  12. customDry in vacuo at 110° C.

Sources & evidence

ORD record
ord-14f02bf997a64a2f9b1e37f3e8064ae9
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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