Réaction #47585

Équation de réaction

(S)-2-benzyloxycarbonylamino-succinic acid 1-methyl ester

carbonyldiimidazole

malonic acid mono t-butyl ester

magnesium ethoxide

→

(S)-2-benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-t-butyl ester 1-methyl ester

Rendement 75.1%

Solvants

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   AutreIn a flask under argon was placed
2. 2
   AutreIn a separate round bottom flask was placed
3. 3
   Concentrationconcentrated in vacuo
4. 4
   workup.ADDITIONadded to the flask
5. 5
   workup.ADDITIONcontaining the succinic acid and carbonyldiimidazole mixture
6. 6
   workup.STIRRINGstirred at 25° C. for 16 h
7. 7
   ConcentrationThe mixture was concentrated in vacuo
8. 8
   Autrepartitioned between diethyl ether (200 mL)
9. 9
   LavageThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (150 mL)
10. 10
    Séchagedried over sodium sulfate
11. 11
    Concentrationconcentrated
12. 12
    AutrePurification by flash column chromatography (silica gel 60, 230-400 mesh; 40% ethyl acetate/hexanes)

Mode opératoire

In a flask under argon was placed (S)-2-benzyloxycarbonylamino-succinic acid 1-methyl ester (3.0 g, 10.67 mmol) and tetrahydrofuran (50 mL). To this mixture was added carbonyldiimidazole (1.90 g, 11.74 mmol) and the resulting mixture was stirred at 25° C. for 6 h. In a separate round bottom flask was placed malonic acid mono t-butyl ester (1.98 g, 11.74 mmol), tetrahydrofuran (30 mL) and magnesium ethoxide (685 mg, 5.87 mmol) and the resulting mixture stirred at 25° C. for 1 h and then concentrated in vacuo. The residue was taken up in tetrahydrofuran (15 mL) and added to the flask containing the succinic acid and carbonyldiimidazole mixture and stirred at 25° C. for 16 h. The mixture was concentrated in vacuo and partitioned between diethyl ether (200 mL) and a 0.5N aqueous hydrochloric acid solution (200 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (150 mL), dried over sodium sulfate and concentrated. Purification by flash column chromatography (silica gel 60, 230-400 mesh; 40% ethyl acetate/hexanes) afforded (S)-2-benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-t-butyl ester 1-methyl ester (3.04 g, 75%) as a pale yellow oil.

Source