(2S)-1-Methyl-2-pyrrolidinemethanol → 3-((S)-1-Methyl-pyrrolidin-2-ylmethoxy)-5-trifluoromethyl-pyridine

HRID 617318

Reaction equation

HRID 617318 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][OH:8].Cl[C:10]1[CH:11]=[N:12][CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][O:8][C:10]1[CH:11]=[N:12][CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1

Participants

4

Reactant 2

HCID 643492(2S)-1-Methyl-2-pyrrolidinemethanolHCID 27366983-Chloro-5-(trifluoromethyl)pyridine

Product 1

HCID 213096373-((S)-1-Methyl-pyrrolidin-2-ylmethoxy)-5-trifluoromethyl-pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-(-)-1-Methyl-2-pyrrolidinemethanol (Aldrich Chemical Co., 0.5 g, 4.34 mmol) was reacted with 3-chloro-5-trifluoromethylpyridine according to the method of Example 3, except using DMF in place of THF as solvent and reducing reaction time to less than 2 hours. The solvent was removed, the residue dissolved in ethyl acetate, and the product purified by chromatography over silica gel to give 170 mg of the title compound. MS (DCI/NH3) m/e: 261 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.50 (d, J=0.6 Hz, 1H), 8.49 (d, J=3.0 Hz, 1H), 7.41 (dd, J=0.6 Hz, 1H), 8.49 (d, J=3.0 Hz, 1H), 7.41 (dd, J=0.6, 3.0 Hz, 1H), 4.12-3.96 (m, 2H), 3.21-3.10 (m, 1H), 2.80-2.65 (m, 1H), 2.51 (s, 3H), 2.44 (m, 1H), 2.14-1.73 (m, 4H).

Workup

  1. customreaction time to less than 2 hours
  2. customThe solvent was removed
  3. dissolutionthe residue dissolved in ethyl acetate
  4. customthe product purified by chromatography over silica gel

Sources & evidence

ORD record
ord-a2c5bbee618b47bebd42ab6da98b33df
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Linked notes

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