反応 #68982

反応方程式

sodium t-butoxide

3-(4-Bromophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

1-methanesulfonylpiperazine

S-Phos

→

3-[4-(4-methanesulfonylpiperazin-1-yl)phenyl]-3,8-diazabicyclo[3.2.1]-octane-8-carboxylic acid tert-butyl ester

収率 97.9%

溶媒

toluene

反応条件

後処理

1. 1
   温度at reflux for 1 h 30
2. 2
   その他After hydrolysis
3. 3
   抽出with a saturated aqueous NaHCO3 solution, and extraction with ethyl acetate
4. 4
   洗浄the organic phase is washed with a saturated aqueous sodium chloride solution
5. 5
   乾燥dried over MgSO4
6. 6
   その他The crude product obtained
7. 7
   その他is chromatographed on silica gel, elution

実験手順

3-(4-Bromophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.64 g, 1.7 mmol), 1-methanesulfonylpiperazine (0.43 g, 2.6 mmol), tris-(dibenzylideneacetone)dipalladium (0.069 g, 0.07 mmol), S-Phos (0.11 g, 0.28 mmol), and sodium t-butoxide (0.25 g, 2.6 mmol) are placed in 10 ml of toluene under nitrogen. The reaction medium is stirred at reflux for 1 h 30. After hydrolysis with a saturated aqueous NaHCO3 solution, and extraction with ethyl acetate, the organic phase is washed with a saturated aqueous sodium chloride solution and dried over MgSO4. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol/ethyl acetate in dichloromethane ranging from 100/0/0 to 7/2.5/0.5 (dichloromethane/ethyl acetate/methanol). 0.75 g of expected 3-[4-(4-methanesulfonylpiperazin-1-yl)phenyl]-3,8-diazabicyclo[3.2.1]-octane-8-carboxylic acid tert-butyl ester is obtained.

出典