Reaction #72734

Reaction equation

sodium carbonate

1-methyl-4-pyrazolylboronic acid

(−)-5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]octane

→

(−)-5-[2-(1-methyl-1H-pyrazol-4-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]octane

Yield 93.2%

Solvents

toluene

ethanol

Conditions

Workup

1. 1
   TemperatureIt is cooled to room temperature
2. 2
   Otherthe solvent is evaporated off under reduced pressure
3. 3
   Filtrationfiltered through diatomaceous earth
4. 4
   ConcentrationThe solvent is concentrated under reduced pressure
5. 5
   Otherthe residue is purified by chromatography on a column of silica gel
6. 6
   Washeluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions

Procedure

0.162 g (0.78 mmol) of 1-methyl-4-pyrazolylboronic acid, 0.160 g (0.6 mmol) of (−)-5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]octane (obtained by reacting 5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]octane (−)-hydrobromide (1:1), prepared in step 1.2, with saturated aqueous sodium carbonate solution) are successively introduced into a 10 ml three-necked round-bottomed flask, as a solution in 3 ml of toluene and 0.3 ml of ethanol. 0.035 g (0.03 mmol) of tetrakis(triphenylphosphine)palladium and 0.6 ml of aqueous 2M sodium carbonate solution are then added and the mixture is heated at 105° C. for 18 hours. It is cooled to room temperature, the solvent is evaporated off under reduced pressure and the residue is taken up in 10 ml of chloroform and filtered through diatomaceous earth. The solvent is concentrated under reduced pressure and the residue is purified by chromatography on a column of silica gel, eluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions. 0.15 g of (−)-5-[2-(1-methyl-1H-pyrazol-4-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]octane is obtained, and is dissolved in 2 ml of isopropyl alcohol to add 0.196 ml of a 5.7N solution of hydrobromic acid in acetic acid. The crystals obtained are collected by filtration and dried under vacuum. 0.163 g of product is obtained.

Source