反応 #2810

反応方程式

sodium cyanoborohydride

sodium cyanoborohydride

L-leucine tert-butyl ester hydrochloride

2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-formyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester

→

title compound

収率 63.0%

2-{2-[2-(1,3-Dioxo-1,3,dihydro-isoindol-2-yl)-2-(2-trimethylsilanyl-ethoxycarbonyl)-ethyl]-benzylamino}-4-methyl-valeric acid, tert-butyl ester

収率 63.0%

溶媒

tetrahydrofuran

methanol

反応条件

後処理

1. 1
   workup.STIRRINGstir for 5 hours
2. 2
   ろ過Filter
3. 3
   ろ過through filter aid
4. 4
   その他evaporate the solvent in vacuo
5. 5
   その他partition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL)
6. 6
   乾燥Dry (Na2SO4)
7. 7
   その他evaporate the solvent in vacuo
8. 8
   その他purify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate)

実験手順

Dissolve 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(2-formyl-phenyl)-propionic acid, 2-trimethylsilanyl-ethyl ester (250 mg, 0.590 mmol) in methanol (15 mL) and treat with L-leucine tert-butyl ester hydrochloride (0.66 g, 3.0 mmol). Stir at room temperature for 2 hours with 3A molecular sieves, add sodium cyanoborohydride (0.6 mL of a 1.0M solution in tetrahydrofuran, 0.6 mmol), stir for 0.5 hours, add additional sodium cyanoborohydride (0.3 mL) and stir for 5 hours. Filter through filter aid, evaporate the solvent in vacuo and partition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL). Dry (Na2SO4), evaporate the solvent in vacuo and purify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate) to give the title compound (221 mg, 63%).

出典