Hydrochloric Acid → 2-(2-Fluoro-4-trifluoromethyl-phenyl)-ethylamine hydrochloride

HRID 216182Notes

Reaction equation

HRID 216182 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]#[N:14].[ClH:15]>CCO.[Pd]>[ClH:15].[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][CH2:13][NH2:14]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 27375972-Fluoro-4-(trifluoromethyl)phenylacetonitrile

Product 1

HCID 690667332-(2-Fluoro-4-trifluoromethyl-phenyl)-ethylamine hydrochlorideYield 78%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

2-Fluoro-4-trifluoromethyl-phenyl acetonitrile (2 g, 9.85 mmol) is hydrogenated with H2 in a balloon, 10% Pd/C (522 mg, 5 mol %) in 95% EtOH (50 mL) containing concentrated hydrochloric acid (1.64 mL) at room temperature for 15 hours. The mixture is filtered and filtrate is concentrated to a solid that is washed with diethyl ether to obtain 2-(2-fluoro-4-trifluoromethyl-phenyl)-ethylamine hydrochloride (1.88 g, 78%) as a solid. LC/MS: 208 (M+H). This compound (1.8 g, 8.7 mmol) is dissolved in EtOH (25 mL) and treated with 4,6-dichloro-2-methoxy-pyrimidine [1.3 g, 7.25 mmol, Intermediate (4)] and sodium bicarbonate (1.52 g, 18.13 mmol). The mixture is heated to reflux for 5 hours. Solid is filtered and EtOH is removed in vacuo. The residue is washed with small amount of DCM to obtain (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2-fluoro-4-trifluoromethyl-phenyl)-ethyl]-amine (2.59 g, 76%) as a solid. LC/MS: 350 (M+H).

Workup

  1. filtrationThe mixture is filtered
  2. concentrationfiltrate is concentrated to a solid
  3. washthat is washed with diethyl ether

Sources & evidence

ORD record
ord-f2b50ec0f3a146ea82de000f95cd0dd9
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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