Ethanol → 3-[1-(2,3-Dichlorophenoxy)-3-methylsulfanylpropyl]pyrrolidine

HRID 1254998Notes

Reaction equation

HRID 1254998 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([CH:13]([OH:18])[CH2:14][CH2:15][S: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[Cl:29].CCO>CN(C=O)C.Cl>[Cl:21][C:22]1[C:23]([Cl:29])=[CH:24][CH:25]=[CH:26][C:27]=1[O:18][CH:13]([CH:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[CH2:14][CH2:15][S:16][CH3:17]

Participants

7

Reactant 4

HCID 702EthanolHCID 24758Sodium hydride2×HCID 119011Benzene, 1,2-dichloro-3-fluoro-HCID 668597603-(1-Hydroxy-3-methylsulfanylpropyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Product 1

HCID 581202633-[1-(2,3-Dichlorophenoxy)-3-methylsulfanylpropyl]pyrrolidine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

3-(1-Hydroxy-3-methylsulfanylpropyl)pyrrolidine-1-carboxylic acid t-butyl ester (49 mg, 180 mmol) was dissolved in DMF (550 μL). 60% NaH in oil (60:40, NaH:mineral oil, 8.5 mg, 210 μmol) was slowly added, and the mixture was stirred for 15 minutes at room temperature. 1,2-Dichloro-3-fluorobenzene (62 μL, 530 μmol) was added, and the resulting mixture was heated at 90° C. for 24 hours. The reaction was quenched with MeOH, and DMF/MeOH was removed in vacuo. The product was dissolved in 1.25M HCl in EtOH (1.4 mL, 1.8 mmol) and stirred overnight at room temperature. The product was then purified by preparative HPLC to yield the title compound as a mixture of all 4 stereoisomers (R,R, R,S, S,S, and S,R) as mono-TFA salts (20 mg, 100% purity). MS m/z: [M+H]+ calcd for C14H19Cl2NOS, 320.06. found 320.0.

Workup

  1. temperaturethe resulting mixture was heated at 90° C. for 24 hours
  2. customThe reaction was quenched with MeOH, and DMF/MeOH
  3. customwas removed in vacuo
  4. stirringstirred overnight at room temperature
  5. customThe product was then purified by preparative HPLC

Sources & evidence

ORD record
ord-f292b0e4231d40778223fddf3fe3aa8c
Source dataset
uspto-grants-2013_06
Patent number
US08455665B2

Reaction notes

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