3-Chloro-4-methylaniline → HCID 59376130, compound

Participants

Reaction Conditions

Reaction Steps

Me3Al (290 μL, 0.57 mmol, 2M in toluene) was added to a solution of the 3-Chloro-4-methylphenylamine (65 mg, 0.46 mmol) in dry dichloroethane (1 mL) at ambient temperature. Stirred for 20 minutes, then (2R,3S)-2-(4-Cyclopentylaminophenyl)-1-(2-methylbenzoyl)piperidine-3-carboxylic acid ethyl ester (100 mg, 0.23 mmol) dissolved in dry dichloroethane (1 mL) was added to it. The reaction mixture was then heated to 85° C. for 3 h, cooled to r.t, diluted with CH2Cl2 (20 mL), washed with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (20 mL) and the combined organic layer was dried (MgSO4) and concentrated. The residue was purified by reverse phase preparative HPLC (20-95% gradient of CH3CN—H2O with 0.1% TFA as additive), the product containing fractions were pooled together and concentrated. The residue was diluted with CH2Cl2 (30 mL), washed with saturated aqueous NaHCO3 solution. The CH2Cl2 layer was dried (MgSO4) and concentrated to get the pure (2R,3S)-2-(4-Cyclopentylaminophenyl)-1-(2-methylbenzoyl)piperidine-3-carboxylic acid (3-chloro-4-methylphenyl)amide in 50% yield.

Provenance & Evidence