N-methyl-2-(trifluoromethyl)aniline

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.00 g (5.71 mmole) of 2-(methylamino)benzotrifluoride, 9 mL (17.3 mmole) of 1.93M phosgene in toluene, and 10 mL of toluene was stirred under N2 for a hour and then treated with 20 mL of 2.5N sodium hydroxide (aqueous). The layers were separated, and the organic phase was concentrated in vacuo to yield 1.12 g (83%) of the title compound as a clear oil, which eventually solidified after prolonged standing: mp 44°-46° C.; homogeneous by TLC in 3:1 hexane-EtOAc; IR spectrum νCO 1750 cm-1 ; FAB-MS m/e 237 (M+1)+. The layers were separated the organic phase was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.00 g (5.71 mmole) of 2-(methylamino)benzotrifluoride, 9 mL (17.3 mmole) of 1.93M phosgene in toluene, and 10 mL of toluene was stirred under N2 for a hour and then treated with 20 mL of 2.5N sodium hydroxide (aqueous). The layers were separated, and the organic phase was concentrated in vacuo to yield 1.12 g (83%) of the title compound as a clear oil, which eventually solidified after prolonged standing: mp 44°-46° C.; homogeneous by TLC in 3:1 hexane-EtOAc; IR spectrum νCO 1750 cm-1 ; FAB-MS m/e 237 (M+1)+. The layers were separated the organic phase was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(methylamino)benzotrifluride (0.870 g, 5.000 mmol), 1-Boc-4-piperidone (1.500 g, 7.500 mmol)), acetic acid (1.5 mL, 17.5 mmol) and sodium triacetoxy borohydride (2.420 g, 11.000 mmol) in 1,2-dichloroethane (30 mL) was stirred at ambient temperature for 2 days. The reaction was quenched with water. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic phase was washed with water, brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromatography to afford 4-[methyl-(2-trifluoromethylphenyl)amino]piperidine-1-carboxylic acid tert-butyl ester (0.360 g, 20%). 1H NMR (300 MHz, CDCl3) δ 7.58 (dd, J=1.2, 7.8 Hz, 1H), 7.48-7.14 (m, 3H), 4.08-4.00 (m, 2H), 2.95-2.87 (m, 2H), 2.68-2.58 (m, 5H), 1.72-1:67 (m, 1H). The reaction was quenched with water The organic phase was separated the aqueous phase was extracted with dichloromethane The combined organic phase was washed with water, brine dried over anhydrous Na2SO4 concentrated The residue was purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(methylamino)benzotrifluride (0.870 g, 5.000 mmol), 1-Boc-4-piperidone (1.500 g, 7.500 mmol)), acetic acid (1.5 mL, 17.5 mmol) and sodium triacetoxy borohydride (2.420 g, 11.000 mmol) in 1,2-dichloroethane (30 mL) was stirred at ambient temperature for 2 days. The reaction was quenched with water. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic phase was washed with water, brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromatography to afford 4-[methyl-(2-trifluoromethylphenyl)amino]piperidine-1-carboxylic acid tert-butyl ester (0.360 g, 20%). 1H NMR (300 MHz, CDCl3) δ 7.58 (dd, J=1.2, 7.8 Hz, 1H), 7.48-7.14 (m, 3H), 4.08-4.00 (m, 2H), 2.95-2.87 (m, 2H), 2.68-2.58 (m, 5H), 1.72-1:67 (m, 1H). The reaction was quenched with water The organic phase was separated the aqueous phase was extracted with dichloromethane The combined organic phase was washed with water, brine dried over anhydrous Na2SO4 concentrated The residue was purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.00 g (5.71 mmole) of 2-(methylamino)benzotrifluoride, 9 mL (17.3 mmole) of 1.93M phosgene in toluene, and 10 mL of toluene was stirred under N2 for a hour and then treated with 20 mL of 2.5N sodium hydroxide (aqueous). The layers were separated, and the organic phase was concentrated in vacuo to yield 1.12 g (83%) of the title compound as a clear oil, which eventually solidified after prolonged standing: mp 44°-46° C.; homogeneous by TLC in 3:1 hexane-EtOAc; IR spectrum νCO 1750 cm-1 ; FAB-MS m/e 237 (M+1)+. The layers were separated the organic phase was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(methylamino)benzotrifluride (0.870 g, 5.000 mmol), 1-Boc-4-piperidone (1.500 g, 7.500 mmol)), acetic acid (1.5 mL, 17.5 mmol) and sodium triacetoxy borohydride (2.420 g, 11.000 mmol) in 1,2-dichloroethane (30 mL) was stirred at ambient temperature for 2 days. The reaction was quenched with water. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic phase was washed with water, brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromatography to afford 4-[methyl-(2-trifluoromethylphenyl)amino]piperidine-1-carboxylic acid tert-butyl ester (0.360 g, 20%). 1H NMR (300 MHz, CDCl3) δ 7.58 (dd, J=1.2, 7.8 Hz, 1H), 7.48-7.14 (m, 3H), 4.08-4.00 (m, 2H), 2.95-2.87 (m, 2H), 2.68-2.58 (m, 5H), 1.72-1:67 (m, 1H). The reaction was quenched with water The organic phase was separated the aqueous phase was extracted with dichloromethane The combined organic phase was washed with water, brine dried over anhydrous Na2SO4 concentrated The residue was purified by flash chromatography