Reaction #561321

Reaction equation

Na2CO3

(4S,5R)-4-(5-bromo-pyrimidin-2-yloxy)-1-aza-bicyclo[3.3.1]nonane

5-Indolyl boronic acid

→

(4S,5R)-4-[5-(1H-indol-5-yl)-pyrimidin-2-yloxy]-1-aza-bicyclo[3.3.1]nonane

Yield 67.0%

Solvents

H2O

toluene EtOH

Conditions

Workup

1. 1
   TemperatureAfter cooling to rt the mixture
2. 2
   Filtrationis filtered over hyflo
3. 3
   Extractionthe filtrate is extracted with water and brine
4. 4
   Dryingthe combined organic layers are dried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Otherthe filtrate is evaporated
7. 7
   OtherThe resulting crude product is purified by FC (255 g silica gel, eluent AcOEt/MeOH/Et3N 70:27:3) and recrystallization from EtOH

Procedure

5.19 g (17.4 mmol) of (4S,5R)-4-(5-bromo-pyrimidin-2-yloxy)-1-aza-bicyclo[3.3.1]nonane is dissolved in 200 ml toluene/EtOH 9:1. 5-Indolyl boronic acid (3.47 g, 21.6 mmol), Pd(PPh3)4 (1.04 g, 0.873 mmol) and a soln. of Na2CO3 (7.38 g, 69.6 mmol) in 35 ml H2O is added. The reaction mixture is stirred at 90° C. for 15 h. After cooling to rt the mixture is filtered over hyflo, the filtrate is extracted with water and brine. The aq. layers are reextracted with AcOEt and the combined organic layers are dried over Na2SO4, filtered and the filtrate is evaporated. The resulting crude product is purified by FC (255 g silica gel, eluent AcOEt/MeOH/Et3N 70:27:3) and recrystallization from EtOH to give 3.87 g (67%) (4S,5R)-4-[5-(1H-indol-5-yl)-pyrimidin-2-yloxy]-1-aza-bicyclo[3.3.1]nonane. MS (ES+): m/e=335 (MR+), m.p. 195-199° C.

Source