Hydrogen Bromide → HCID 23599484, compound

HRID 1350904Notes

Reaction equation

HRID 1350904 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[S:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23]C)[CH:18]=3)=[CH:15][CH:16]=1)=[O:11])[CH2:2]2.Br.C(=O)([O-])[O-].[Na+].[Na+].Cl>C(O)(=O)C>[N:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[C@@H:3]([NH:9][C:10]([C:12]1[S:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=3)=[CH:15][CH:16]=1)=[O:11])[CH2:2]2

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 10340Sodium Carbonate2×HCID 23599485HCID 23599485, compound

Product 1

HCID 23599484HCID 23599484, compoundYield 3.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To the (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(3-methoxyphenyl)thiophene-2-carboxamide) (900 mg), 48% aqueous hydrobromic acid (10 mL) and glacial acetic acid (10 mL) were added. After heating under reflux for 4 h, saturated aqueous sodium carbonate and solid sodium carbonate were added to adjust to pH 10. The aqueous layer was extracted with chloroform and the combined extracts were dried over magnesium sulfate. After filtration and evaporation, residue was purified by flash chromatography using 5%–20% 3.5M methanolic ammonia/chloroform mixtures as the eluent. The product obtained was purified by reverse phase HPLC on a Waters Bondapak® C18 column using a gradient of acetonitrile and 0.1% aqueous trifluoroacetic acid as the eluent. The hydrochloride salt was prepared by evaporation of the product-containing fractions, dissolution of the residue in methanol, addition of excess hydrogen chloride solution (1M in diethyl ether) and evaporation. Recrystallisation from methanol/diethyl ether gave the hydrochloride salt of the title compound as a colourless solid (32 mg); MS (ES+) 329 (MH+).

Workup

  1. temperatureAfter heating
  2. temperatureunder reflux for 4 h
  3. extractionThe aqueous layer was extracted with chloroform
  4. dry with materialthe combined extracts were dried over magnesium sulfate
  5. filtrationAfter filtration and evaporation, residue
  6. customwas purified by flash chromatography
  7. customThe product obtained
  8. customwas purified by reverse phase HPLC on a Waters Bondapak® C18 column
  9. customThe hydrochloride salt was prepared by evaporation of the product-containing fractions, dissolution of the residue in methanol
  10. customRecrystallisation from methanol/diethyl ether

Sources & evidence

ORD record
ord-be689f78ed714defa25853c0a3facba4
Source dataset
uspto-grants-2007_05
Patent number
US07214688B2

Reaction notes

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