反応 #69716

反応方程式

n-Butyl lithium

5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester

1-methyl-4-piperidone

→

5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester

溶媒

THF

反応条件

後処理

1. 1
   workup.STIRRINGstirred at −78° C. for a further 60 minutes
2. 2
   その他The reaction was quenched with saturated ammonium chloride solution
3. 3
   抽出then extracted with EtOAc
4. 4
   洗浄The EtOAc layer was washed with saturated NaHCO3, brine
5. 5
   乾燥dried (MgSO4)
6. 6
   その他evaporated
7. 7
   その他Purification by flash column chromatography
8. 8
   洗浄on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia/DCM

実験手順

0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at −78° C. under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 μl; 1.2 equiv.) was added and stirred at −78° C. for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia/DCM gave 111 mg of 5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a colourless oil.

出典