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

HRID 1254996Notes

Reaction equation

HRID 1254996 reaction equation
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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

(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.

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-c0791482eb094400b7c8035f36011a7c
Source dataset
uspto-grants-2013_06
Patent number
US08455665B2

Reaction notes

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