반응 #2810

반응 방정식

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

수율 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

수율 63.0%

용매

tetrahydrofuran

methanol

반응 조건

후처리

1. 1
   workup.STIRRINGstir for 5 hours
2. 2
   여과Filter
3. 3
   여과through filter aid
4. 4
   기타evaporate the solvent in vacuo
5. 5
   기타partition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL)
6. 6
   건조Dry (Na2SO4)
7. 7
   기타evaporate the solvent in vacuo
8. 8
   기타purify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate)

실험 절차

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%).

출처