Hydrogen chloride-ethyl acetate → HCID 67321470, compound

HRID 1184190Notes

Reaction equation

HRID 1184190 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:16]([N:18]([CH2:38][CH:39]([CH3:41])[CH3:40])[C@H:19]1[CH2:24][C@@H:23]([C:25]2[O:29][N:28]=[C:27]([CH3:30])[N:26]=2)[CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]1)=[O:17].C(OCC)(=O)C.[ClH:48]>>[ClH:48].[ClH:48].[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:16]([N:18]([C@H:19]1[CH2:24][C@@H:23]([C:25]2[O:29][N:28]=[C:27]([CH3:30])[N:26]=2)[CH2:22][NH:21][CH2:20]1)[CH2:38][CH:39]([CH3:41])[CH3:40])=[O:17]

Participants

3

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 67026107HCID 67026107, compound

Product 1

HCID 67321470HCID 67321470, compound

Procedure

(3R, 55)-1-(tert-Butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (265 mg), N-hydroxy acetamidine (56 mg), 1H-benzotriazol-1-ol (95 mg) and N,N-diisopropylethylamine (259 μl)) were dissolved in DMF (10 ml), WSC.HCl (144 mg) was added and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in toluene (15 ml), and the mixture was refluxed under heating for 15 hr. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:1) was concentrated under reduced pressure to give tert-butyl(3S, 5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(3-methyl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate (324 mg). The obtained tert-butyl(3S, 5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(3-methyl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate was dissolved in 4M hydrogen chloride-ethyl acetate (5 ml), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated, and the residue was diluted with aqueous sodium bicarbonate, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue was dissolved in methanol (3 ml), 4M Hydrogen chloride-ethyl acetate (1 ml) was added and the mixture was stirred for 5 min. The solvent was evaporated under reduced pressure to give the object product (74 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with aqueous sodium bicarbonate
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. washa fraction eluted with ethyl acetate
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionThe residue was dissolved in methanol (3 ml)
  10. addition4M Hydrogen chloride-ethyl acetate (1 ml) was added
  11. stirringthe mixture was stirred for 5 min
  12. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-02c1948a421149a8bf23053379a6a156
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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