Reacción #2810

Ecuación de reacción

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

Rendimiento 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

Rendimiento 63.0%

Disolventes

tetrahydrofuran

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGstir for 5 hours
2. 2
   FiltraciónFilter
3. 3
   Filtraciónthrough filter aid
4. 4
   Otroevaporate the solvent in vacuo
5. 5
   Otropartition the residue between methylene chloride (100 mL) and saturated sodium hydrogen carbonate (40 mL)
6. 6
   SecadoDry (Na2SO4)
7. 7
   Otroevaporate the solvent in vacuo
8. 8
   Otropurify by silica gel chromatography (5:1 hexane/ethyl acetate followed by 3:1 hexane/ethyl acetate)

Procedimiento

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%).

Fuente