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

HRID 588001

Reaction equation

HRID 588001 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:18])[CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:9]1)=O)(C)(C)C.CN(C=O)C.[H-].[Na+].[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29](F)[C:28]=1[Cl:34].Cl.CCO>>[Cl:26][C:27]1[C:28]([Cl:34])=[CH:29][CH:30]=[CH:31][C:32]=1[O:18][C@H:13]([C@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[CH2:14][CH:15]([CH3:16])[CH3:17]

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 702EthanolHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 119011Benzene, 1,2-dichloro-3-fluoro-HCID 57347268(S)-tert-Butyl 3-((S)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylate

Product 1

HCID 58104615(S)-3-[(S)-1-(2,3-Dichlorophenoxy)-3-methylbutyl]pyrrolidine

Procedure

(S)-3-((S)-1-Hydroxy-3-methylbutyl)pyrrolidine-1-carboxylic acid t-butyl ester (50 mg, 0.2 mmol) was dissolved in DMF (940 μL, 12 mmol). Sodium hydride (5.6 mg, 233 μmol) was then slowly added, and the mixture was stirred at room temperature for 15 minutes. 1,2-Dichloro-3-fluoro-benzene (64.1 mg, 388 μmol) was added. The mixture was stirred at 70° C. for 3 hours, then concentrated under vacuum. 1.2M HCl in EtOH (1.1 mL, 1.3 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 (37.4 mg, 100% purity). MS m/z: [M+H] calcd for C15H21Cl2NO, 302.10. found 302.2.

Workup

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

Sources & evidence

ORD record
ord-ea772d7fbd544f2d9875e6ede11e87a1
Source dataset
uspto-grants-2016_01
Patent number
US09227933B2

Linked notes

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