Sodium Carbonate → 1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-(3,4-dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidine

HRID 343494Notes

Reaction equation

HRID 343494 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].C(=O)([O-])[O-].[Na+].[Na+].[CH3:25][O:26][C:27]1[CH:35]=[CH:34][C:33]([N:36]2[CH:40]=[N:39][N:38]=[N:37]2)=[CH:32][C:28]=1[C:29](Cl)=[O:30].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.C(OCC)(=O)C>[CH3:25][O:26][C:27]1[CH:35]=[CH:34][C:33]([N:36]2[CH:40]=[N:39][N:38]=[N:37]2)=[CH:32][C:28]=1[C:29]([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:30]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 153920213-(3,4-Dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidineHCID 153920222-Methoxy-5-(1H-tetrazol-1-yl)benzoyl Chloride

Product 1

HCID 153920231-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-(3,4-dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
-5 °C

Procedure

Combine 3-(3,4-dimethoxyphenyl)--3-(2-hydroxyethyl)pyrrolidine (5.34 g, 21.2 mmol) and sodium carbonate (1.24 g, 11.7 mmol) in ethyl acetate/water (4/1) (120 mL). Cool the reaction mixture to -5° C. with an salt-ice bath. Slowly, add 2-methoxy-5-(1H-tetrazol-1-yl)benzoyl chloride (22.3 mmol) as a solution in ethyl acetate (60 mL) at a rate such that the temperature of the reaction mixture does not rise above 0° C. Maintain the reaction temperature at about 0° C. After 18 hours, separate the organic layer. Extract the organic layer twice with 1M aqueous hydrochloric acid solution, saturated solution of sodium bicarbonate, water and a saturated solution of sodium chloride. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Combine the aqueous layers and neutralize with a saturated solution of sodium bicarbonate. Extract the neutralized aqueous layers with dichloromethane. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain the title compound.

Workup

  1. customdoes not rise above 0° C
  2. temperatureMaintain the reaction temperature at about 0° C
  3. customseparate the organic layer
  4. extractionExtract the organic layer twice with 1M aqueous hydrochloric acid solution, saturated solution of sodium bicarbonate, water
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto obtain a residue
  9. extractionExtract the neutralized aqueous layers with dichloromethane
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-2f24aaeaba7e454188292907b8c8edf4
Source dataset
uspto-grants-1999_01
Patent number
US05861417

Reaction notes

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