Ethanol → (S)-3-[(R)-1-(3-Chloro-2-trifluoromethylphenoxy)-2-ethylsulfanylethyl]-pyrrolidine

HRID 1254994Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1254994
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:18])[CH2:14][S:15][CH2:16][CH3:17])[CH2:9]1)=O)(C)(C)C.[H-].[Na+].[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24](F)[C:23]=1[C:29]([F:32])([F:31])[F:30].CCO>CN(C=O)C.Cl>[Cl:21][C:22]1[C:23]([C:29]([F:30])([F:31])[F:32])=[C:24]([CH:25]=[CH:26][CH:27]=1)[O:18][C@H:13]([C@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[CH2:14][S:15][CH2:16][CH3:17]

Komponenten

7

Edukt 4

HCID 702EthanolHCID 24758Sodium hydrideHCID 167439801-Chloro-3-fluoro-2-(trifluoromethyl)benzeneHCID 66859941(S)-3-((R)-2-Ethylsulfanyl-1-hydroxyethyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Produkt 1

HCID 50899714(S)-3-[(R)-1-(3-Chloro-2-trifluoromethylphenoxy)-2-ethylsulfanylethyl]-pyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(S)-3-((R)-2-Ethylsulfanyl-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester (10 mg, 40 μmol) was dissolved in DMF (174 μL). NaH (1.3 mg, 54.5 μmol) was added and the mixture was stirred at room temperature for 15 minutes. 2-Chloro-6-fluorobenzotrifluoride (21.6 mg, 109 μmol) was added and the mixture was stirred at 100° C. for 1 hour. The mixture was cooled to room temperature, concentrated then dissolved in 1.2M HCl in EtOH (890 μL, 1.1 mmol) and stirred overnight at room temperature. The product was concentrated and the crude product was dissolved in 1:1 AcOH/H2O (1.5 mL) then purified by preparative HPLC to yield the title compound as a mono-TFA salt (3.4 mg, purity 97%). MS m/z: [M+H]+ calcd for C15H19ClF3NOS, 354.08. found 354.0.

Aufarbeitung

  1. stirringthe mixture was stirred at 100° C. for 1 hour
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated
  4. stirringstirred overnight at room temperature
  5. concentrationThe product was concentrated
  6. dissolutionthe crude product was dissolved in 1:1 AcOH/H2O (1.5 mL)
  7. customthen purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-18ac2f362fda4fe09a483b6cc6589209
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455665B2

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