Réaction #159449

Équation de réaction

3-(2,4-dioxobicyclo[3.2.1]oct-3-yl)-4-ethylphenylboronic acid

potassium phosphate

2-bromo-5-chloropyridine

tris(3-sulfophenyl)phosphine trisodium salt

→

3-[5-(5-chloropyridin-2-yl)-2-ethylphenyl]bicyclo[3.2.1]octane-2,4-dione

Solvants

water acetonitrile

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONis then added
2. 2
   Autreby flushing with nitrogen
3. 3
   Températurebefore heating at 160° C. under microwave irradiation for 15 minutes
4. 4
   TempératureAfter cooling to room temperature the reaction
5. 5
   Autreis partitioned between 2M aqueous hydrochloric acid and dichloromethane
6. 6
   Autrethe organic phase is separated
7. 7
   ExtractionThe aqueous phase is further extracted with dichloromethane
8. 8
   Autreall organic fractions are combined then evaporated
9. 9
   AutreThe residue is purified by preparative reverse-phase HPLC

Mode opératoire

To a microwave vial containing 3-(2,4-dioxobicyclo[3.2.1]oct-3-yl)-4-ethylphenylboronic acid (0.15 g, 0.52 mmol) and potassium phosphate (0.667 g, 3.15 mmol) is added 2-bromo-5-chloropyridine (0.121 g, 0.63 mmol), palladium acetate (4.0 mg, 0.016 mmol) and tris(3-sulfophenyl)phosphine trisodium salt (21 mg, 0.038 mmol). A degassed solvent mixture of water/acetonitrile (1.6 ml, 2:1 ratio) is then added, followed by flushing with nitrogen, then stirring at ambient temperature for 5 minutes before heating at 160° C. under microwave irradiation for 15 minutes. After cooling to room temperature the reaction is partitioned between 2M aqueous hydrochloric acid and dichloromethane, and the organic phase is separated. The aqueous phase is further extracted with dichloromethane and all organic fractions are combined then evaporated. The residue is purified by preparative reverse-phase HPLC to give 3-[5-(5-chloropyridin-2-yl)-2-ethylphenyl]bicyclo[3.2.1]octane-2,4-dione.

Source