Ethyl Acetate → (S)-1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine

HRID 323442Notes

Reaction equation

HRID 323442 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].C(=O)(O)[O-].[Na+].[CH3:52][O:53][C:54]1[CH:62]=[CH:61][C:60]([N:63]2[CH:67]=[N:66][N:65]=[N:64]2)=[CH:59][C:55]=1[C:56](Cl)=[O:57].C(OCC)(=O)C>CC(C)=O.O.CC(C)=O.CO.ClCCl>[CH3:52][O:53][C:54]1[CH:62]=[CH:61][C:60]([N:63]2[CH:67]=[N:66][N:65]=[N:64]2)=[CH:59][C:55]=1[C:56]([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:57]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 153920222-Methoxy-5-(1H-tetrazol-1-yl)benzoyl ChlorideHCID 131720896(S)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid

Product 1

HCID 53771624(S)-1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 18366337Propan-2-one--water (1/1)SolventHCID 21226129Dichloromethane methanolSolvent2×

Procedure

Combine (S)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt (1.20 g, 1.77 mmol) and sodium bicarbonate (0.75 g, 8.9 mmol) in acetone/water (5 mL/5 mL). Cool in an ice bath. Add 2-methoxy-5-(1H-tetrazol-1-yl)benzoyl chloride (0.37 g, 1.6 mmol) in acetone (20 mL). After 30 minutes, warm to ambient temperature. After 5 hours, filter the reaction mixture and extract the filtrate with ethyl acetate. Extract the organic layer 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/dichloromethane, and then 6% methanol/dichloromethane to give the title compound: Rf=0.38 (silica gel, 6% methanol/dichloromethane).

Workup

  1. temperatureCool in an ice bath
  2. waitAfter 5 hours
  3. filtrationfilter the reaction mixture
  4. extractionextract the filtrate with ethyl acetate
  5. extractionExtract the organic layer 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-e42e908f6fbf4d72876be8aa33998dcf
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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