反応 #69718

反応方程式

4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride

triethylamine

2,4-bis-benzyloxy-5-isopropenyl-benzoic acid

EDC

HOAt

→

(2,4-bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone

収率 55.2%

溶媒

THF

DMF

DCM

EtOAc

反応条件

後処理

1. 1
   workup.STIRRINGthe reaction was then stirred at room temperature overnight
2. 2
   洗浄washed with water, 1N NaOH and brine
3. 3
   その他the EtOAc layer was separated
4. 4
   乾燥dried (MgSO4)
5. 5
   その他evaporated
6. 6
   その他Purification by flash column chromatography
7. 7
   洗浄on SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM

実験手順

A solution of 2,4-bis-benzyloxy-5-isopropenyl-benzoic acid (145 mg; 1.2 equiv.) in DCM (5 ml) was treated with EDC (80 mg; 1.3 equiv.) and HOAt (66 mg; 1.5 equiv.) then stirred at room temperature for 30 minutes. This solution was then added to a mixture of 4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride (112 mg; 0.32 mmol) and triethylamine (90 μl; 2 equiv.) in THF (5 ml) and DMF (2 ml), the reaction was then stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, washed with water, 1N NaOH and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM gave 104 mg of (2,4-bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone as a yellow glass.

出典