Boron tribromide → 1-(2-hydroxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

HRID 323367Notes

Reaction equation

HRID 323367 reaction equation
C[O:2][C:3]1[CH:24]=[CH:23][C:22]([N:25]2[CH:29]=[N:28][N:27]=[N:26]2)=[CH:21][C:4]=1[C:5]([N:7]1[CH2:11][CH2:10][C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([CH2:12][CH2:13][OH:14])[CH2:8]1)=[O:6].B(Br)(Br)Br.CO.ClCCl.C1(C)C=CC=CC=1.CO>ClCCl>[OH:2][C:3]1[CH:24]=[CH:23][C:22]([N:25]2[CH:29]=[N:28][N:27]=[N:26]2)=[CH:21][C:4]=1[C:5]([N:7]1[CH2:11][CH2:10][C:9]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)([CH2:12][CH2:13][OH:14])[CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 25134Boron tribromideHCID 184644561-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidineHCID 21226129Dichloromethane methanolHCID 21867641Toluene methanol

Product 1

HCID 184650361-(2-hydroxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Combine 1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) (2.0 g, 5.1 mmol) and anhydrous dichloromethane (100 mL). Cool in an ice bath. Add a solution of boron tribromide (17.8 mL, 1 M, 17.8 mmol) and stir. After 2 hours, pour the reaction mixture into ice-water and stir vigorously. After 18 hours, separate the layers and extract the organic layer with water. Saturate the aqueous layer with sodium chloride and extract with dichloromethane. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia to give a residue. Combine the residue and toluene/methanol. Evaporate invacao to give a residue, dissolve in dichloromethane, filter, evaporate, combine with dichloromethane, again evaporate to remove residual toluene to give the title compound: mp; 86-96° C. Rf=0.37 (silica gel, 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia).

Workup

  1. temperatureCool in an ice bath
  2. stirringstir vigorously
  3. waitAfter 18 hours
  4. customseparate the layers
  5. extractionextract the organic layer with water
  6. concentrationSaturate the aqueous layer with sodium chloride
  7. extractionextract with dichloromethane
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. customevaporate in vacuo
  11. customto give a residue
  12. customEvaporate invacao
  13. customto give a residue
  14. filtrationfilter
  15. customevaporate
  16. customagain evaporate
  17. customto remove residual toluene

Sources & evidence

ORD record
ord-2c6da1d73a1d4f7bb93d57cefe0e7557
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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