Реакция #159446

Уравнение реакции

tris(3-sulfophenyl)phosphine trisodium salt

4-chloro-3-methylphenyl boronic acid

3-(5-bromo-2-ethyl-phenyl)-bicyclo[3.2.1]octane-2,4-dione

potassium phosphate

→

3-(4′-chloro-4-ethyl-3′-methylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione

Растворители

acetonitrile

Условия реакции

Обработка

1. 1
   workup.DISTILLATIONdistilled water (1.6 ml, 1:1 ratio)
2. 2
   workup.ADDITIONis next added (
3. 3
   Промывкаwashing-down any solids from the slides of the vial),
4. 4
   Другоеflushing with nitrogen
5. 5
   ТемператураAfter cooling to room temperature the reaction mixture
6. 6
   workup.ADDITIONis diluted with N,N-dimethylformamide (1 ml)
7. 7
   Другоеpartitioned between 2M hydrochloric acid and dichloromethane
8. 8
   ДругоеAfter the organic phase is separated the aqueous phase
9. 9
   Промывкаis again washed with dichloromethane
10. 10
    Концентрированиеconcentrated in vacuo
11. 11
    Другоеto afford a crude gum
12. 12
    ДругоеThis crude product is then purified by preparative reverse-phase HPLC

Методика

To a microwave vial is added palladium(II) acetate (3.7 mg, 0.016 mmol), tris(3-sulfophenyl)phosphine trisodium salt (23 mg, 0.041 mmol), 4-chloro-3-methylphenyl boronic acid (0.167 g, 0.97 mmol), 3-(5-bromo-2-ethyl-phenyl)-bicyclo[3.2.1]octane-2,4-dione (0.209 g, 0.65 mmol) and potassium phosphate (0.691 g, 3.26 mmol). A degassed mixed solution of acetonitrile/distilled water (1.6 ml, 1:1 ratio) is next added (washing-down any solids from the slides of the vial), followed by stirring for 5 minutes and flushing with nitrogen. This mixture is then heated at 160° C. under microwave irradiation for 15 minutes. After cooling to room temperature the reaction mixture is diluted with N,N-dimethylformamide (1 ml), then partitioned between 2M hydrochloric acid and dichloromethane. After the organic phase is separated the aqueous phase is again washed with dichloromethane, then all organic fractions are combined and concentrated in vacuo to afford a crude gum. This crude product is then purified by preparative reverse-phase HPLC to afford 3-(4′-chloro-4-ethyl-3′-methylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione.

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