methyl 4-(anilinomethyl)benzoate

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 4-((phenylamino)methyl)benzoate (800 mg, 3.2 mmol), lithium hydroxide monohydrate (72 mg, 3 mmol), tetrahydrofuran (6 mL), methanol (2 mL) and water (2 mL) was stirred at 20° C. for 2 hours. The mixture was acidified to pH=1 with concentrated hydrochloric acid and then extracted with ethyl acetate (15 mL×3). The combined organic phase was separated, dried by sodium sulfate and then filtered. The filtrate was concentrated in vacuo to give 4-((phenylamino)methyl)benzoic acid (600 mg, 80%). The product was used for the next step directly without further purification. LRMS (M+H+) m/z: calcd 227.09. found 227. extracted with ethyl acetate (15 mL×3) The combined organic phase was separated dried by sodium sulfate filtered The filtrate was concentrated in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 4-formylbenzoate (1 g, 6 mmol) and aniline (837 mg, 9 mmol) were dissolved in methanol (30 mL). The mixture was heated to 50° C., and acetic acid (two or three drop) was added to the reaction mixture. The resultant mixture was stirred at 50° C. for 1 hour. After the mixture was cooled to room temperature, sodium cyanoborohydride (1.13 g, 18 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction was quenched with water (10 mL) and the mixture was extracted with dichloromethane (10 mL×3). The combined organic phase was separated, dried by sodium sulfate and then filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=8:1) to give methyl 4-((phenylamino)methyl)benzoate (0.8 g, 55%). LRMS (M+H+) m/z: cald. 241.08. found 241. LRMS (M+H+) m/z: calcd 241.08. found 241. 1H NMR (300 MHz, CD3OD): δ 7.95 (dd, J=7.2 Hz, J=2.1 Hz, 2H), 7.44 (d, J=7.8 Hz, 2H), 7.05 (t, J=6.0 Hz, 2H), 6.60-6.56 (m, 3H), 4.37 (s, 2H), 3.86 (s, 3H). After the mixture was cooled to room temperature The reaction was quenched with water (10 mL) the mixture was extracted with dichloromethane (10 mL×3) The combined organic phase was separated dried by sodium sulfate filtered The filtrate was concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=8:1)