Sodium Hydroxide → 1-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine

HRID 1682962Notes

Reaction equation

HRID 1682962 reaction equation
C([C@](C(O)=O)(O)[C@](C(=O)C1C=CC(OC)=CC=1)(O)C(O)=O)(=O)C1C=CC(OC)=CC=1.[Cl:31][C:32]1[CH:33]=[C:34]([C:39]2([CH2:44][CH2:45][OH:46])[CH2:43][CH2:42][NH:41][CH2:40]2)[CH:35]=[CH:36][C:37]=1[Cl:38].[OH-].[Na+].[C:49](=[O:52])(O)[O-].[Na+].[CH3:54][O:55][C:56]1[CH:64]=[CH:63][C:59]([C:60](Cl)=[O:61])=[C:58](OC)[C:57]=1[O:67][CH3:68]>ClCCl.C(OCC)(=O)C.CC(C)=O>[CH3:68][O:67][C:57]1[CH:58]=[C:59]([CH:63]=[C:64]([O:52][CH3:49])[C:56]=1[O:55][CH3:54])[C:60]([N:41]1[CH2:42][CH2:43][C:39]([C:34]2[CH:35]=[CH:36][C:37]([Cl:38])=[C:32]([Cl:31])[CH:33]=2)([CH2:44][CH2:45][OH:46])[CH2:40]1)=[O:61]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 27608082,3,4-trimethoxybenzoyl chlorideHCID 131720034HCID 131720034, compound

Product 1

HCID 184644171-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine (+)-3-(3,4-dichloro-phenyl)-3-(2-hydroxyethyl)-pyrrolidine (R, R)-di-p-anisoyltartaric acid salt (772.7 g, 1140 mmol) and acetone (5 L). Cool in to 0°-10° C. and add aqueous sodium hydroxide solution (46 g, 1105 mmol, in 5 L of water). Add sodium bicarbonate (479 g, 5700 mmol). While maintaining the temperature at 0°-10° C., add dropwise over 30 minutes, trimethoxy-benzoyl chloride (262.9 g, 1140 mmol). After 3 hours, add ethyl acetate (5 L) and allow to warm to ambient temperature. Separate the layers and extract the aqueous layer 3 times with ethyl acetate. Combine the organic layers and extract 1M sodium hydroxide solution, 1M hydrochloric acid solution, and then saturated aqueous sodium bicarbonate solution. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Treat the residue with dichloromethane and evaporate in vacuo the title compound: Rf =0.36 (silica gel, 6% methanol/dichloromethane).

Workup

  1. temperatureCool in to 0°-10° C.
  2. temperatureWhile maintaining the temperature at 0°-10° C.
  3. additionadd dropwise over 30 minutes
  4. customSeparate the layers
  5. extractionextract the aqueous layer 3 times with ethyl acetate
  6. extractionextract 1M sodium hydroxide solution, 1M hydrochloric acid solution
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give a residue
  11. customevaporate in vacuo the title compound

Sources & evidence

ORD record
ord-af8ef4e3f8f043feaf6d97b51dee9064
Source dataset
uspto-grants-1997_06
Patent number
US05635510

Reaction notes

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