Sodium hydride → (S)-2-(1-methylpyrrolidin-3-yloxy)-5-(trifluoromethyl)benzonitrile

HRID 717262

Reaction equation

HRID 717262 reaction equation
F[C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[C:4]#[N:5].[H-].[Na+].[CH3:16][N:17]1[CH2:21][CH2:20][C@H:19]([OH:22])[CH2:18]1>O1CCCC1>[CH3:16][N:17]1[CH2:21][CH2:20][C@H:19]([O:22][C:2]2[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=2[C:4]#[N:5])[CH2:18]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5210162-Fluoro-5-(trifluoromethyl)benzonitrileHCID 6435041-Methyl-3-pyrrolidinol, (+)-

Product 1

HCID 66698243(S)-2-(1-methylpyrrolidin-3-yloxy)-5-(trifluoromethyl)benzonitrileYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-fluoro-5-(trifluoromethyl)benzonitrile (8.0 g, 42.3 mmol, Aldrich) in tetrahydrofuran (50 mL) were added sodium hydride (1.9 g, 46.5 mmol, 60% in mineral oil) and (S)-1-methylpyrrolidin-3-ol (4.7 mL, 46.5 mmol, Aldrich). After stirring at room temperature for 3 h, the reaction mixture was quenched with saturated NaHCO3 (30 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 10.9 g of the title compound. MS (ESI+) m/z 271 (M+H)+.

Workup

  1. customthe reaction mixture was quenched with saturated NaHCO3 (30 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a65ef246cb8346178943125bdaafaeec
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Linked notes

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