Reaction #640615

Reaction equation

(4S,5R)-acetic acid 1-aza-bicyclo[3.3.1]non-4-yl ester

→

(4S,5R)-1-aza-bicyclo[3.3.1]nonan-4-ol

Yield 91.3%

Solvents

NaOH

Conditions

Workup

1. 1
   TemperatureAfter cooling to rt
2. 2
   Extractionthe mixture is extracted with THF/brine
3. 3
   DryingThe organic layer is dried over Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Otherthe filtrate is evaporated

Procedure

(4S,5R)-acetic acid 1-aza-bicyclo[3.3.1]non-4-yl ester (5.45 g, 29.7 mmol) is dissolved in 10% aq. NaOH soln. and stirred for 1 h at 50° C. After cooling to rt, the mixture is extracted with THF/brine. The organic layer is dried over Na2SO4, filtered and the filtrate is evaporated to give 3.83 g (91%) of (4S,5R)-1-aza-bicyclo[3.3.1]nonan-4-ol, which is dissolved in 50 ml THF and cooled to 0° C. NHMDS (35 ml of 1 M THF soln.) is added dropwise, the reaction mixture is stirred at rt for 0.5 h and then added to a precooled soln. (−15° C.) of 5-bromo-2-chloro-pyrimidine (5.89 g, 30.5 mmol) in THF. The mixture is stirred for 15 h at rt, then diluted with THF and extracted with 1M aq. NaOH soln. and brine. The aq. layers are 2× reextracted with THF, the combined organic layers are dried over Na2SO4, filtered and the filtrate is evaporated. The resulting crude product (10.15 g) is recrystallized from CH3CN/MeOH to give 5.21 g (65%) of (4S,5R)-4-(5-bromo-pyrimidin-2-yloxy)-1-aza-bicyclo[3.3.1]nonane.

Source