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

HRID 2390580Notes

Reaction equation

HRID 2390580 reaction equation
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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-a188e45fbcad47a5a327de6cfb680af2
Source dataset
uspto-grants-2012_09
Patent number
US08273786B2

Reaction notes

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