Ethyl Acetate → 1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

HRID 323357Notes

Reaction equation

HRID 323357 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.[C:31]1([C:37]2([CH2:42][CH2:43][OH:44])[CH2:41][CH2:40][NH:39][CH2:38]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)(O)[O-].[Na+].[CH3:50][O:51][C:52]1[CH:60]=[CH:59][C:58]([N:61]2[CH:65]=[N:64][N:63]=[N:62]2)=[CH:57][C:53]=1[C:54](Cl)=[O:55].C(OCC)(=O)C>CC(C)=O.O.CC(C)=O.CO.C(OCC)(=O)C>[CH3:50][O:51][C:52]1[CH:60]=[CH:59][C:58]([N:61]2[CH:65]=[N:64][N:63]=[N:62]2)=[CH:57][C:53]=1[C:54]([N:39]1[CH2:40][CH2:41][C:37]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([CH2:42][CH2:43][OH:44])[CH2:38]1)=[O:55]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 153920222-Methoxy-5-(1H-tetrazol-1-yl)benzoyl ChlorideHCID 70109704(-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

Product 1

HCID 184644561-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 18366337Propan-2-one--water (1/1)SolventHCID 21584119Ethylacetate methanolSolvent2×

Procedure

Add (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt (6.72 g, 11.0 mmol) and sodium bicarbonate (4.87 g, 58 mmol) in acetone/water (50 mL/50 mL). Cool in an ice bath. Add a solution of 2-methoxy-5-(1H-tetrazol-1-yl)benzoyl chloride (1.66 g, 9.9 mmol) in acetone (100 mL). After 30 minutes, warm to ambient temperature. After 60 hours, filter the reaction mixture and dilute the filtrate with ethyl acetate. Extract the filtrate with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give residue. Chromatograph the residue on silica gel eluting sequentially with ethyl acetate, 3% methanol/ethyl acetate, and then 5% methanol/ethyl acetate to give the title compound: Rf=0.48 (5% methanol/dichloromethane).

Workup

  1. temperatureCool in an ice bath
  2. waitAfter 60 hours
  3. filtrationfilter the reaction mixture
  4. additiondilute the filtrate with ethyl acetate
  5. extractionExtract the filtrate with a saturated aqueous sodium bicarbonate solution
  6. dry with materialDry the organic layer over MgSO4
  7. filtrationfilter
  8. customevaporate in vacuo
  9. customto give residue

Sources & evidence

ORD record
ord-7ad8846c5c8e4e0eac0ad3034374efbc
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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