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

HRID 2390582Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2390582
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:19])[CH2:14][S:15][CH:16]([CH3:18])[CH3:17])[CH2:9]1)=O)(C)(C)C.[H-].[Na+].[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25](F)[C:24]=1[C:30]([F:33])([F:32])[F:31].CCO>CN(C=O)C.Cl>[Cl:22][C:23]1[C:24]([C:30]([F:31])([F:32])[F:33])=[C:25]([CH:26]=[CH:27][CH:28]=1)[O:19][C@H:13]([C@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[CH2:14][S:15][CH:16]([CH3:17])[CH3:18]

Komponenten

7

Edukt 4

HCID 702EthanolHCID 24758Sodium hydrideHCID 167439801-Chloro-3-fluoro-2-(trifluoromethyl)benzeneHCID 66859623(S)-3-((R)-1-Hydroxy-2-isopropylsulfanylethyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Produkt 1

HCID 58120258(S)-3-[(R)-1-(3-Chloro-2-trifluoromethylphenoxy)-2-isopropylsulfanylethyl]pyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(S)-3-((R)-1-Hydroxy-2-isopropylsulfanylethyl)pyrrolidine-1-carboxylic acid t-butyl ester (10 mg, 0.030 μmol) was dissolved in DMF (166 μL). NaH (1.7 mg, 69.1 μmol) was added and the mixture was stirred at room temperature for 15 minutes. 2-Chloro-6-fluorobenzotrifluoride (20.6 mg, 104 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 (1.0 mL, 1.2 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 (9.2 mg, purity 94%). MS m/z: [M+H]+ calcd for C16H21ClF3NOS, 368.10; found 368.0.

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-c7566a1f09874d98b70f3c6082277db7
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08273786B2

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