Reaktion #73903

Reaktionsgleichung

isopropylchloroformate

N-[1-(benzofuran-5-yl)-2-(dimethylamino)-2-oxoethyl]-L-leucine

(2R)-[(tert-butoxycarbonyl)amino](2,3-dihydro-1H-inden-2-yl)ethanoic acid

N-methylmorpholine

→

(2R)-2-(benzofuran-5-yl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide

Ausbeute 7.3%

Lösungsmittel

toluene

dimethylformamide

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 20 hours
2. 2
   Sonstigethe solvent was removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue was dissolved in 4N hydrochloric acid in dioxan (4 ml)
4. 4
   workup.ADDITIONAfter 4 hours methanol (13 ml) was added
5. 5
   workup.WAITthe reaction was left
6. 6
   workup.WAITto stand for a further 18 hours
7. 7
   SonstigeThe solvent was then removed in vacuo
8. 8
   Sonstigethe residue was separated between dichloromethane and saturated sodium bicarbonate solution
9. 9
   SonstigeThe organic phase was evaporated in vacuo
10. 10
    WaschenThe product was eluted

Vorschrift

To a solution of (2R)-[(tert-butoxycarbonyl)amino](2,3-dihydro-1H-inden-2-yl)ethanoic acid (419 mg) in dry tetrahydrofuran (5 ml) at −20° C. under a nitrogen atmosphere was added N-methylmorpholine (158 μl) and a solution of isopropylchloroformate in toluene (1.0M, 1.44 ml). After 10 minutes, a solution of N-[1-(benzofuran-5-yl)-2-(dimethylamino)-2-oxoethyl]-L-leucine (478 mg) in dimethylformamide (5 ml) was added and the reaction was allowed to warm to room temperature. After 20 hours, the solvent was removed in vacuo and the residue was dissolved in 4N hydrochloric acid in dioxan (4 ml). After 4 hours methanol (13 ml) was added and the reaction was left to stand for a further 18 hours. The solvent was then removed in vacuo and the residue was separated between dichloromethane and saturated sodium bicarbonate solution. The organic phase was evaporated in vacuo and the residue was applied to an SPE (10 g, silica). The product was eluted using an ethyl acetate:methanol gradient (3:1 to 1:3) to afford (2R)-2-(benzofuran-5-yl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide (51 mg).

Quelle