Aluminium lithium hydride → 2-(4-Fluorophenyl)-2-methylpropan-1-amine

HRID 409348Notes

Reaction equation

HRID 409348 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH3:12])([CH3:11])[CH2:9][NH2:10])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 212511052-(4-Fluorophenyl)-2-methylpropanenitrile

Product 1

HCID 212510232-(4-Fluorophenyl)-2-methylpropan-1-amineYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-fluorophenylacetonitrile (50 g, 370 mmol, 1.0 equiv) and iodomethane (70 mL, 1.11 mol, 3 equiv) in THF (370 mL) was added KOt-Bu (124 g, 1.1 mol, 3 equiv) as a solid in portions such that the reaction mixture did not exceed 50° C. The reaction mixture was stirred overnight and then quenched by the addition of brine. The mixture was diluted with EtOAc and washed twice with brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to provide 2-(4-fluorophenyl)-2-methylpropanenitrile as a yellow oil (57 g, 94%), which was used without further purification in the next step. To a solution of the nitrile in dry THF (800 mL) was added a solution of LAH (210 mL, 2 M in ether, 420 mmol, 1.2 equiv). After mixture was heated to reflux overnight, the reaction was allowed to cool to room temperature followed by a Fieser and Fieser work-up. Filtration of the resulting solids provided the title compound as an orange oil (57 g, 92%). m/z=168.1 [M+H]+.

Workup

  1. customwas used without further purification in the next step
  2. temperatureAfter mixture was heated
  3. temperatureto reflux overnight
  4. filtrationFiltration of the resulting solids

Sources & evidence

ORD record
ord-c85e735f04cf4c0481c6de019eb258fb
Source dataset
uspto-grants-2014_06
Patent number
US08759380B2

Reaction notes

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