Реакция #2810

Уравнение реакции

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

Выход 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

Выход 63.0%

Растворители

tetrahydrofuran

methanol

Условия реакции

Обработка

1. 1
   workup.STIRRINGstir for 5 hours
2. 2
   ФильтрацияFilter
3. 3
   Фильтрацияthrough filter aid
4. 4
   Другоеevaporate the solvent in vacuo
5. 5
   Другоеpartition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL)
6. 6
   СушкаDry (Na2SO4)
7. 7
   Другоеevaporate the solvent in vacuo
8. 8
   Другоеpurify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate)

Методика

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%).

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