Dicyclohexylcarbodiimide → (3-ethyl-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 1255020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1255020
C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.Cl.[CH2:27]([C:29]1[CH:30]=[C:31]([NH:35][CH:36]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:37]([OH:39])=[O:38])[CH:32]=[CH:33][CH:34]=1)[CH3:28].[N:46]12[CH2:53][CH2:52][CH:49]([CH2:50][CH2:51]1)[C@@H:48](O)[CH2:47]2>C1COCC1>[N:46]12[CH2:53][CH2:52][CH:49]([CH2:50][CH2:51]1)[C@@H:48]([O:38][C:37](=[O:39])[CH:36]([NH:35][C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([CH2:27][CH3:28])[CH:30]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:47]2

Komponenten

6

Edukt 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67425860(3-Ethyl-phenylamino)-phenyl-acetic acid hydrochloride

Produkt 1

HCID 46840575(3-ethyl-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

PS-DCC (1097 mg, 1.371 mmol, loading: 1.25 mmol/g) is suspended in THF (15 mL). HOBT (210 mg, 1.37 mmol), (3-ethyl-phenylamino)-phenyl-acetic acid hydrochloride (I42) (200 mg, 0.68 mmol), and (R)-quinuclidin-3-ol (262 mg, 2.06 mmol) are added and the suspension is shaken at RT for 16 hours. PS-DCC is filtered off and the filtrate is evaporated. The resulting residue is dissolved in EtOAc and washed with water, sat. NaHCO3, water and brine. The organic phase is dried over Na2SO4, filtered and evaporated. The crude is purified by flash chromatography (DCM/MeOH=95/5) to obtain the title compound as a colorless oil (72 mg, 30% yield, mixture of diastereoisomers).

Aufarbeitung

  1. filtrationPS-DCC is filtered off
  2. customthe filtrate is evaporated
  3. dissolutionThe resulting residue is dissolved in EtOAc
  4. washwashed with water, sat. NaHCO3, water and brine
  5. dry with materialThe organic phase is dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude is purified by flash chromatography (DCM/MeOH=95/5)

Quellen und Nachweise

ORD-Eintrag
ord-1b395ed6fbcf4b31b65584f0770f0c93
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455646B2

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