تفاعل #69716

معادلة التفاعل

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

المذيبات

THF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر