Réaction #57094

Équation de réaction

3,4-dichlorophenyl boronic acid

sodium carbonate

tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate

→

tert-butyl 4-[2-(3′,4′-dichloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate

Rendement 67.0%

Solvants

1,2-dimethoxyethane

Conditions de réaction

Traitement

1. 1
   Températureat reflux until all starting material
2. 2
   Autrewas consumed
3. 3
   Autreprecipitation of black palladium
4. 4
   Autre(3 h)
5. 5
   TempératureAfter cooling
6. 6
   workup.ADDITIONwater was added
7. 7
   Extractionthe reaction mixture was extracted with ethyl acetate (30 mL)
8. 8
   LavageThe organic layer was washed with brine
9. 9
   Séchagedried over sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated
12. 12
    Autreto give a crude solid, which
13. 13
    Autrewas purified via flash column chromatography (silica, gradient from 0% ethyl acetate/hexane to 30% ethyl acetate/hexane)

Mode opératoire

A mixture of tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate (0.72 g, 1.55 mmol) and tetrakis(triphenylphosphine)palladium (37 mg, 0.032 mmol, 10 mol %) in 1,2-dimethoxyethane (30 mL) was stirred for 10 min at room temperature. To this mixture was added sequentially 3,4-dichlorophenyl boronic acid (0.44 g, 2.32 mmol) and a 2M aqueous solution of sodium carbonate (0.8 mL, 1.6 mmol, 5 equivalent), and the mixture was heated at reflux until all starting material was consumed and precipitation of black palladium occurred (3 h). After cooling, water was added and the reaction mixture was extracted with ethyl acetate (30 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude solid, which was purified via flash column chromatography (silica, gradient from 0% ethyl acetate/hexane to 30% ethyl acetate/hexane) to yield 0.55 g (67%) of tert-butyl 4-[2-(3′,4′-dichloro-biphenyl-3-yl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate as a foam, which was used as such in the next step.

Source