Реакция #418306

Уравнение реакции

9-BBN

1-Boc-4-methylene piperidine

4-bromo-1,2-dichlorobenzene

potassium carbonate

NaOH

→

4-(3,4-dichloro-benzyl)-piperidine-1-carboxylic acid tert-butyl ester

Выход 69.0%

Растворители

THF

DMF H2O

water

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was refluxed for 2 h
2. 2
   workup.ADDITIONThe reaction mixture was then added, via cannula, to a preformed solution
3. 3
   Температураcooled to r.t.
4. 4
   Экстракцияextracted with EtOAc (3×)
5. 5
   Сушкаdried (Na2SO4)
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеThe crude residue was purified (FCC)

Методика

1-Boc-4-methylene piperidine (1.32 g, 6.70 mmol) was degassed (neat) for 15 minutes, and then treated with a THF solution of 9-BBN (0.5 M in THF, 13.5 mL, 6.75 mmol). The reaction mixture was refluxed for 2 h, then cooled to r.t. The reaction mixture was then added, via cannula, to a preformed solution consisting of 4-bromo-1,2-dichlorobenzene (1.49 mg, 6.64 mmol), Pd(dppf)Cl2 dichloromethane complex (148 mg, 0.181 mmol), and potassium carbonate (1.20 g, 8.68 mmol) in DMF/H2O (15 mL/1.5 mL). The resultant mixture was heated at 60° C. for 48 h, cooled to r.t., poured into water, basified to pH 11 with 1N NaOH, and extracted with EtOAc (3×). The organic layers were combined, dried (Na2SO4), and concentrated. The crude residue was purified (FCC) to give 4-(3,4-dichloro-benzyl)-piperidine-1-carboxylic acid tert-butyl ester (1.57 g, 69%).

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