تفاعل #57094

معادلة التفاعل

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

المردود 67.0%

المذيبات

1,2-dimethoxyethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةat reflux until all starting material
2. 2
   أخرىwas consumed
3. 3
   أخرىprecipitation of black palladium
4. 4
   أخرى(3 h)
5. 5
   درجة الحرارةAfter cooling
6. 6
   workup.ADDITIONwater was added
7. 7
   استخلاصthe reaction mixture was extracted with ethyl acetate (30 mL)
8. 8
   غسيلThe organic layer was washed with brine
9. 9
   تجفيفdried over sodium sulfate
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated
12. 12
    أخرىto give a crude solid, which
13. 13
    أخرىwas purified via flash column chromatography (silica, gradient from 0% ethyl acetate/hexane to 30% ethyl acetate/hexane)

الإجراء التجريبي

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.

المصدر