Hydrochloric Acid → (S)-3-[(S)-1-(2,3-Dichlorophenoxy)butyl]pyrrolidine

HRID 1671376Notes

Reaction equation

HRID 1671376 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:17])[CH2:14][CH2:15][CH3:16])[CH2:9]1)=O)(C)(C)C.CN(C=O)C.[H-].[Na+].[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28](F)[C:27]=1[Cl:33].Cl.CCO>>[Cl:25][C:26]1[C:27]([Cl:33])=[CH:28][CH:29]=[CH:30][C:31]=1[O:17][C@H:13]([C@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[CH2:14][CH2:15][CH3:16]

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 702EthanolHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 119011Benzene, 1,2-dichloro-3-fluoro-HCID 58104616(S)-3-((S)-1-Hydroxybutyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Product 1

HCID 58104605(S)-3-[(S)-1-(2,3-Dichlorophenoxy)butyl]pyrrolidine

Procedure

(S)-3-((S)-1-Hydroxybutyl)pyrrolidine-1-carboxylic acid t-butyl ester (50 mg, 0.2 mmol) was dissolved in DMF (1.0 mL, 13 mmol). NaH (5.9 mg, 246 μmmol) was slowly added and the mixture was stirred at room temperature for 15 minutes. 1,2-Dichloro-3-fluorobenzene (67.8 mg, 411 μmmol) was added. The mixture was stirred at 70° C. for 3 hours, then concentrated. 1.2M HCl in EtOH (1.0 mL, 1.2 mmol) was added, and the mixture was stirred overnight. The product was concentrated and purified by preparative HPLC to yield the title compound as a mono-TFA salt (19 mg, 100% purity). MS m/z: [M+H]+ calcd for C14H19Cl2NO, 288.08; found 288.0.

Workup

  1. stirringThe mixture was stirred at 70° C. for 3 hours
  2. concentrationconcentrated
  3. stirringthe mixture was stirred overnight
  4. concentrationThe product was concentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-10cbbd61fcf344c68cde93d82568aef8
Source dataset
uspto-grants-2011_08
Patent number
US07994209B2

Reaction notes

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