Hydrochloric Acid → N~1~-(3-Bromophenyl)ethane-1,2-diamine

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-bromoaniline (0.50 g, 2.9 mmol) in diethyl ether (Et2O, 5 mL) was added 4 M HCl in dioxane (1 mL), and the mixture was stirred at 25° C. for 1 h. Solvent was removed under reduced pressure, and the resulting HCl salt was dissolved in 2-(2-methoxyethoxy)ethanol (2 mL). 2-Oxazolidinone (0.429 g, 4.93 mmol) was added, and the reaction mixture was heated to 180° C. for 24 h. The collected crude solid was purified by column chromatography (0-10% (1% NH4OH in MeOH)/CH2Cl2) to provide N1-(3-bromo-phenyl)-ethane-1,2-diamine (0.10 g, 16%). 3-(Piperidine-1-carbonyl)-benzaldehyde (Example 1, step D; 0.091 g, 0.42 mmol) was added to a solution of the phenyl-diamine in 1,2-dichloroethane (10 mL), and the reaction mixture was stirred at 25° C. for 15 min. The mixture was treated with NaBH(OAc)3 (0.128 g, 0.604 mmol), and the resulting suspension was stirred at 25° C. for 18 h. The suspension was partitioned with satd NH4Cl (20 mL) and CH2Cl2 (20 mL), and the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography (2-10% CH3OH/CH2Cl2), and then by preparative TLC (10% CH3OH/CH2Cl2) to provide the desired product (0.060 g, 34%). MS (ESI): mass calculated for C21H26BrN3O, 415.13; m/z found, 416.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.28-7.26 (m, 3H), 7.21-7.16 (m, 1H), 6.93 (t, J=8.0 Hz, 1H), 6.74-6.71 (m, 1H), 6.67 (t, J=2.0 Hz, 1H), 6.47-6.44 (m, 1H), 4.23 (br s, 1H), 3.75 (s, 2H), 3.64 (br s, 2H), 3.25 (br s, 2H), 3.10 (t, J=5.6 Hz, 2H), 2.83-2.80 (m, 2H), 1.60-1.43 (m, 6H).

Provenance & Evidence