Reaktion #69716

Reaktionsgleichung

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

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle