Water → methyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoate

HRID 877312Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 877312
Cl.[NH2:2][C@@H:3]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[O:7][CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1.[C:28](Cl)(=[O:38])[O:29][C@@H:30]1[CH:35]2[CH2:36][CH2:37][N:32]([CH2:33][CH2:34]2)[CH2:31]1.O>N1C=CC=CC=1>[C:22]1([C@H:3]([NH:2][C:28]([O:29][C@@H:30]2[CH:35]3[CH2:36][CH2:37][N:32]([CH2:33][CH2:34]3)[CH2:31]2)=[O:38])[C:4]2[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=2)[O:7][CH2:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Komponenten

5

Edukt 3

HCID 962WaterHCID 20812191(R)-quinuclidin-3-yl carbonochloridateHCID 86720812(S)-Methyl 4-((3-(amino(phenyl)methyl)phenoxy)methyl)benzoate hydrochloride

Produkt 1

HCID 86720814methyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoateAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of (S)-methyl 4-((3-(amino(phenyl)methyl)phenoxy)methyl)-benzoate hydrochloride (12.0 g, 31.3 mmol) in pyridine (100 mL) at 0° C. was added portion-wise (R)-quinuclidin-3-yl carbonochloridate (8.50 g, 37.5 mmol). The reaction was stirred at 0° C. for 1 hour and then allowed to warm to RT for 16 hours. Water was added to the reaction mixture and extracted with ethyl acetate (×3). The combined extracts were washed with brine, dried (sodium sulfate), filtered and the solvent evaporated at reduced pressure. The crude material was purified by chromatography on a KP-NH Biotage cartridge eluting with 0-20% methanol in ethyl acetate to afford the title compound (10.3 g, 66%).

Aufarbeitung

  1. temperatureto warm to RT for 16 hours
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customthe solvent evaporated at reduced pressure
  7. customThe crude material was purified by chromatography on a KP-NH Biotage cartridge
  8. washeluting with 0-20% methanol in ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-8a3aa38fc8cf48c4be94a55fdf3192a5
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987299B2

Notizen zur Reaktion

Wird geladen…