Ethanol → (S)-3-[(R)-2-Ethoxy-1-(naphthalen-1-yloxy)ethyl]pyrrolidine

HRID 533385Notes

Reaction equation

HRID 533385 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:18])[CH2:14][O:15][CH2:16][CH3:17])[CH2:9]1)=O)(C)(C)C.F[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1.[H-].[Na+].CCO>CN(C=O)C.Cl>[CH2:16]([O:15][CH2:14][C@@H:13]([C@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[O:18][C:28]1[C:29]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:25]=[CH:26][CH:27]=1)[CH3:17]

Participants

7

Reactant 4

HCID 702EthanolHCID 94501-FluoronaphthaleneHCID 24758Sodium hydrideHCID 66858889(S)-3-((R)-2-Ethoxy-1-hydroxyethyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Product 1

HCID 58120253(S)-3-[(R)-2-Ethoxy-1-(naphthalen-1-yloxy)ethyl]pyrrolidine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

(S)-3-((R)-2-Ethoxy-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester (200 mg, 0.8 mmol) and 1-fluoronaphthalene were dissolved in DMF (2.7 mL). NaH (27.8 mg, 1.2 mmol) was added and the mixture was stirred at room temperature for 15 minutes, then heated at 120° C. for 4 hours. The mixture was then cooled to room temperature. The mixture was concentrated then dissolved in 1.2M HCl in EtOH (19 mL, 23 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 (125 mg, 94% purity). MS m/z: [M+H]+ calcd for C18H23NO2, 286.17. found 286.2.

Workup

  1. temperatureheated at 120° C. for 4 hours
  2. temperatureThe mixture was then cooled to room temperature
  3. concentrationThe mixture was concentrated
  4. stirringstirred overnight at room temperature
  5. concentrationThe product was concentrated
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-f75c8874f2fc43f2b07c0d3fe5cb7e7b
Source dataset
uspto-grants-2014_10
Patent number
US08853255B2

Reaction notes

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