Activated Cl Displacement

Examples:

Example 1

The chloride (30 g, 125 mmol) and the amine (18.22 g, 125 mmol) were suspended in n-BuOH (300 mL). The mixture was then treated with 4 N HCl in dioxane (25 mL, 100 mL) and refluxed at 100 C for 90 min under N2. The reaction was cooled to RT, diluted with diethyl ether, and the resulting solid was filtered and dried to provide the product as a pale yellow solid. [29 g, 67%] [WO2010038081, page 89]

Example 2

A mixture of the amine (200 mg, 1 mmol), the chloride (149 mg, 1 mmol), and DIEA (129 mg 1 mmol), in NMP (2 mL) was heated to 80 C. Concentrated in vacuo and purified the crude by FC (30 -100% EtOAc/hexane) to provide the product as a clear oil (187 mg, 60 %). [WO2010016005, page 80]

Example 3

A solution of the chloride (1.0 equiv), the amine (1.0 equiv), and DIEA (1.5 equiv) in NMP (0.1 M) was heated at 140 C for 48 h. Upon cooling the solution was poured onto ice and upon melting of the ice the solid was filtered, rinsed with H2O, and dried to provide the product. [WO2010026121, page 52]

Example 4

A mixture of CsF (178 mg, 1.17 mmol), the chloride (100 mg, 0.43 mmol), and the amine (130 mg, 0.65 mmol), in DMSO (0.9 mL) was heated to 120 C overnight. The crude product was filtered and purified by HPLC (water/ACN with AcOH). [WO2010016005, page 84]