Reacción #162591

Ecuación de reacción

3-(2-Chloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

4-aminophenylboronic acid

Na2CO3

→

4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)pyrimidin-2-yl]aniline

Rendimiento 82.0%

Disolventes

EtOH

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe mixture is degassed
2. 2
   workup.ADDITIONTetrakis(triphenylphosphine) palladium is added (144 mg, 5 mol %)
3. 3
   Temperaturathe mixture is heated
4. 4
   Temperaturaunder reflux for 48 hours
5. 5
   workup.ADDITIONThe mixture is diluted with EtOAc
6. 6
   Lavadowashed with saturated NaHCO3
7. 7
   Secadothe organic phase is dried (MgSO4)
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated
10. 10
    OtroThe mixture is purified by silica gel chromatography

Procedimiento

3-(2-Chloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (3, 564 mg, 2.5 mmol) and 4-aminophenylboronic acid, pinacol ester (602 mg, 2.75 mmol) are dissolved in toluene (25 mL) and EtOH (15 mL). A 2M solution of Na2CO3 is added (5 mL) and the mixture is degassed by leading a stream of nitrogen through the solution. Tetrakis(triphenylphosphine) palladium is added (144 mg, 5 mol %) and the mixture is heated under reflux for 48 hours. The mixture is diluted with EtOAc, washed with saturated NaHCO3, the organic phase is dried (MgSO4), filtered, and concentrated. The mixture is purified by silica gel chromatography using a gradient of ethyl acetate in hexanes (40-100%) to give 576 mg (2.04 mmol, 82%) of 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)pyrimidin-2-yl]aniline. RT 1.51, M+H=283.1

Fuente