Hydrochloric Acid → N-(piperidin-4-ylmethyl)-3,5-bis(trifluoromethyl)benzamide

Participants

Reaction Steps

To a solution of 1-Boc-4-(aminomethyl)piperidine (18.0 g, 84.1 mmol) and DIPEA (12.9 g, 100 mmol) in anhydrous CH2Cl2 (200 mL) at 15° C. was added 3,5-bis-(trifluoromethyl)benzoyl chloride (23.4 g, 85.0 mmol) slowly. After the reaction mixture was stirred at room temperature for 30 min, water (50 mL) was added followed by adding aqueous HCl (0.5; N, 100 mL). The organic fraction was collected. The aqueous fraction was extracted with CH2Cl2 (100 mL). The combined organic solution was dried over anhydrous Na2SO4 and passed through a silica gel plug. The desired compound was eluted off with EtOAc/petroleum ether (1:3 in v/v). Solvents were removed and the product was dissolved in EtOAc (200 mL). To the solution HCl (g) bubbled for 5 min to form a white suspension. The suspension was stirred at room temperature for 30 min, and then concentrated to around 100 mL. Diethyl ether (150 mL) was added and the suspension was cooled at 7° C. for 1 h. A white HCl salt was collected by filtration. The salt was dissolved in a mixture of methanol/water (30/300 mL), and aqueous NaOH (2 N) was added until pH=˜11. The mixture was extracted with CH2Cl2 (5×200 ML) and the combined organic solution was dried over anhydrous Na2SO4. After filtration the filtrate was concentrated in vacuo to give pale yellow sticky foam (28.8 g, 97%).).

Provenance & Evidence