Hydrochloric Acid → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (3R,5S)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylate dihydrochloride

HRID 2168882Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2168882
C(OC([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:24]3[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=3[N:22]=2)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:36]([OH:38])=[O:37])[CH2:9]1)=O)(C)(C)C.O[CH2:40][C:41]1[O:42][C:43](=[O:47])[O:44][C:45]=1[CH3:46].C1(C)C(S([Cl:57])(=O)=O)=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[ClH:65]>CC(N(C)C)=O.CN(C1C=CN=CC=1)C>[ClH:57].[ClH:65].[CH3:31][O:30][CH2:29][CH2:28][CH2:27][CH2:26][N:25]1[C:24]2[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=2[N:22]=[C:21]1[C:19]([N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C@@H:12]1[CH2:13][NH:8][CH2:9][C@H:10]([C:36]([O:38][CH2:40][C:41]2[O:42][C:43](=[O:47])[O:44][C:45]=2[CH3:46])=[O:37])[CH2:11]1)=[O:20]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 8623o-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 105108784-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-oneHCID 58355779(3R,5S)-(tert-butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid

Produkt 1

HCID 67323140(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (3R,5S)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylate dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

(3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (0.3 g) and 4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one (0.09 g) were dissolved in DMA (3.0 ml), toluenesulfonyl chloride (0.13 g), DMAP (0.014 g) and potassium carbonate (0.1 g) were added with stirring under ice-cooling, and the mixture was stirred for 6 hr under ice-cooling, and further at room temperature overnight. The reaction mixture was neutralized with 1N aqueous hydrochloric acid and extracted with ethyl acetate. The extract was washed successively with aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (0:10→1:1) was concentrated under reduced pressure, and a fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue was dissolved in 2N hydrochloric acid-ethyl acetate solution, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated to give the object product (186 mg).

Aufarbeitung

  1. temperaturecooling
  2. stirringthe mixture was stirred for 6 hr under ice-
  3. temperaturecooling
  4. customfurther at room temperature
  5. customovernight
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed successively with aqueous sodium bicarbonate and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. washa fraction eluted with ethyl acetate-hexane (0:10→1:1)
  11. concentrationwas concentrated under reduced pressure
  12. washa fraction eluted with ethyl acetate
  13. concentrationwas concentrated under reduced pressure
  14. dissolutionThe residue was dissolved in 2N hydrochloric acid-ethyl acetate solution
  15. stirringthe mixture was stirred at room temperature for 1 hr
  16. concentrationThe reaction mixture was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-7ee43448e09b4f499ff3a814277794eb
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045436B2

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