반응 #69716

반응 방정식

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

용매

THF

반응 조건

후처리

1. 1
   workup.STIRRINGstirred at −78° C. for a further 60 minutes
2. 2
   기타The reaction was quenched with saturated ammonium chloride solution
3. 3
   추출then extracted with EtOAc
4. 4
   세척The EtOAc layer was washed with saturated NaHCO3, brine
5. 5
   건조dried (MgSO4)
6. 6
   기타evaporated
7. 7
   기타Purification by flash column chromatography
8. 8
   세척on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia/DCM

실험 절차

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.

출처