Ethanol → (S)-3-[(R)-1-(4-Chloro-2-methylphenoxy)-2-methylsulfanylethyl]pyrrolidine

HRID 2390578Notes

Reaction equation

HRID 2390578 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:17])[CH2:14][S:15][CH3:16])[CH2:9]1)=O)(C)(C)C.[H-].[Na+].[Cl:20][C:21]1[CH:22]=[CH:23][C:24](F)=[C:25]([CH3:27])[CH:26]=1.CCO>CN(C=O)C.Cl>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([O:17][C@H:13]([C@H:10]2[CH2:11][CH2:12][NH:8][CH2:9]2)[CH2:14][S:15][CH3:16])=[C:25]([CH3:27])[CH:26]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 24758Sodium hydrideHCID 27251135-Chloro-2-fluorotolueneHCID 66859519(S)-3-((R)-1-Hydroxy-2-methylsulfanylethyl)pyrrolidine-1-carboxylic acid t-butyl ester

Product 1

HCID 58120257(S)-3-[(R)-1-(4-Chloro-2-methylphenoxy)-2-methylsulfanylethyl]pyrrolidine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

(S)-3-((R)-1-Hydroxy-2-methylsulfanylethyl)pyrrolidine-1-carboxylic acid t-butyl ester (20 mg, 80 μmol) was dissolved in DMF (367 μL). NaH (3.7 mg, 153 μmol) was added and the mixture was stirred at room temperature for 15 minutes. 5-Chloro-2-fluorotoluene (33.2 mg mg, 230 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 (2.2 mL, 2.7 mmol) and stirred overnight at room temperature. The product was concentrated and purified by preparative HPLC to yield the title compound as a mono-TFA salt (0.6 mg, purity 85%). MS m/z: [M+H]+ calcd for C14H20ClNOS, 286.10; found 286.0.

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. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-07e5e0486ce34443826e598274cf7a95
Source dataset
uspto-grants-2012_09
Patent number
US08273786B2

Reaction notes

Loading…