4-Methylmorpholine → HCID 18333552, compound

HRID 1682991Notes

Reaction equation

HRID 1682991 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.[CH2:26]([O:28][C:29]1[CH:30]=[C:31]([CH:35]=[C:36]([O:41][CH2:42][CH3:43])[C:37]=1[O:38][CH2:39][CH3:40])[C:32](Cl)=[O:33])[CH3:27].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:32](=[O:33])[C:31]3[CH:30]=[C:29]([O:28][CH2:26][CH3:27])[C:37]([O:38][CH2:39][CH3:40])=[C:36]([O:41][CH2:42][CH3:43])[CH:35]=3)[CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 12754774HCID 12754774, compoundHCID 153920213-(3,4-Dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidineHCID 18522661Acetone cardice

Product 1

HCID 18333552HCID 18333552, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

2-[3-(3,4-Dimethoxy-phenyl)-pyrrolidin-3-yl]-ethanol (405 mg, 1.61 mmol) and dichloromethane (20 mL) were combined. 4-Methylmorpholine (350 L, 3.22 mmol, 2 eq.) was added. The mixture was cooled in a dry-ice/acetone bath and a solution of 3,4,5-triethoxy-benzoyl chloride (461 mg, 1.69 mmol) in dichloromethane (10 mL) was added dropwise. After the addition was complete, the dry-ice/acetone bath was changed to an ice bath and the mixture was stirred for 1 h. Allowed to warm to ambient temperature and maintained overnight. The solution was extracted with 1N HCl (2×50 mL), saturated NaHCO3 (50 mL), and H2O (50 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 70° C./0.5 Torr for 16 h to obtain the title compound: Rf =0.31 (silica gel, 20:1 ethyl acetate/methanol), mp=139°°141° C.

Workup

  1. temperatureThe mixture was cooled in a dry-ice/acetone bath
  2. additionAfter the addition
  3. temperaturemaintained overnight
  4. extractionThe solution was extracted with 1N HCl (2×50 mL), saturated NaHCO3 (50 mL), and H2O (50 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 70° C./0.5 Torr for 16 h

Sources & evidence

ORD record
ord-3325cff9370d4615884cc0ea1f51e193
Source dataset
uspto-grants-1997_06
Patent number
US05635510

Reaction notes

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