1-Boc-4-(4-chloro-2-fluorophenyl)piperazine synthesis

Yield:945422-81-1 95%

Reaction Conditions:

with tris-(dibenzylideneacetone)dipalladium⁽⁰⁾;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl;sodium tertiary butoxide in toluene at 60;Inert atmosphere;

Steps:

139A Tert-butyl 4-(4-chloro-2-fluorophenyl)piperazine- 1 -carboxylate

Under argon, a solution of l-bromo-4-chloro-2-fluorobenzene (3.80 g, 18.1 mmol) and tert-butyl piperazine- 1-carboxylate (3.38 g, 18.1 mmol) in toluene (38 ml) was treated with Pd2dba3 (166 mg, 181 pmol), rac- BINAP (226 mg, 363 pmol) and sodium tert-butylate (2.44 g, 25.4 mmol) and stirred overnight at 60°C. The reaction mixture was diluted with ethyl acetate, filtered over celite and rinsed with ethyl acetate. The filtrate was evaporated affording 5.86 g (95 % yield) of the tilte compound which was used in the next step without further purification. LC-MS (Method 4): Rt = 2.43 min; MS (ESIpos): m/z = 315 [M+H]⁺

References:

WO2022/122916,2022,A1 Location in patent:Page/Page column 183-184