Ethanol → (R)-3-[(S)-(2,3-Dichlorophenoxy)(tetrahydropyran-4-yl)-methyl]pyrrolidine

HRID 2390576Notes

Reaction equation

HRID 2390576 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]([C@@H:13]([OH:20])[CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH2:9]1)=O)(C)(C)C.[H-].[Na+].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26](F)[C:25]=1[Cl:31].CCO>CN(C=O)C.Cl>[Cl:23][C:24]1[C:25]([Cl:31])=[CH:26][CH:27]=[CH:28][C:29]=1[O:20][C@@H:13]([CH:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)[C@@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1

Participants

7

Reactant 4

HCID 702EthanolHCID 24758Sodium hydrideHCID 119011Benzene, 1,2-dichloro-3-fluoro-HCID 66859077(R)-3-[(S)-Hydroxy(tetrahydropyran-4-yl)methyl]pyrrolidine-1-carboxylic Acid t-Butyl Ester

Product 1

HCID 58120262(R)-3-[(S)-(2,3-Dichlorophenoxy)(tetrahydropyran-4-yl)-methyl]pyrrolidine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-3-[(S)-Hydroxy(tetrahydropyran-4-yl)methyl]pyrrolidine-1-carboxylic acid t-butyl ester (30 mg, 0.1 mmol) was dissolved in DMF (380 μL). NaH (3.0 mg, 126 μmol) was added and the mixture was stirred at room temperature for 15 minutes. 1,2-Dichloro-3-fluorobenzene (34.7 mg, 210 μmol) was added and the mixture was stirred at 100° C. overnight. The mixture was concentrated then dissolved in 1.2M HCl in EtOH (510 μL, 610 μmol) and stirred overnight. The product was concentrated and purified by preparative HPLC to yield the title compound as a mono-TFA salt (10.8 mg, purity 100%). MS m/z: [M+H]+ calcd for C16H21Cl2NO2, 330.10; found 330.0.

Workup

  1. stirringthe mixture was stirred at 100° C. overnight
  2. concentrationThe mixture was concentrated
  3. stirringstirred overnight
  4. concentrationThe product was concentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-506b004417b748b89a1f74a466fdbde9
Source dataset
uspto-grants-2012_09
Patent number
US08273786B2

Reaction notes

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