Реакция #74302

Уравнение реакции

LDA

N-benzoylalanine

carbonyl diimidazole

ethyl acetate

→

ethyl 4-(benzoylamino)-3-oxopentanoate

Выход 95.5%

Растворители

THF

THF

Условия реакции

Обработка

1. 1
   Температураcooled down to −78° C
2. 2
   workup.ADDITIONwas added
3. 3
   workup.STIRRINGThe resulting solution was stirred 30 minutes at −78° C.
4. 4
   workup.STIRRINGThe resulting white slurry was stirred 30 minutes at −78° C.
5. 5
   Температураwarmed up to −10° C
6. 6
   ДругоеThe reaction was quenched with a saturated aqueous solution of NH4Cl
7. 7
   ДругоеPhases were separated
8. 8
   Сушкаthe organics were dried over MgSO4 and solvents
9. 9
   Другоеremoved under reduced pressure
10. 10
    ДругоеThe crude product was carried to the next step without purification

Методика

In the first flask, N-benzoylalanine (2 g, 10.35 mmol) was dissolved in THF (20 mL), and carbonyl diimidazole (CDI) (1.84 g, 11.39 mmol) was added. The resulting mixture was stirred 1 hour at rt and cooled down to −78° C. Into a second flask, ethyl acetate (3.83 g, 43.48 mmol) in THF (40 mL) was cooled down to −78° C. and LDA (24.3 mL, 48.51 mmol, 2 M in THF) pre-cooled to −78° C. was added. The resulting solution was stirred 30 minutes at −78° C., and the lithium enolate generated was cannulated into the first flask. The resulting white slurry was stirred 30 minutes at −78° C. and warmed up to −10° C. The reaction was quenched with a saturated aqueous solution of NH4Cl. Phases were separated and the organics were dried over MgSO4 and solvents removed under reduced pressure. The crude product was carried to the next step without purification. This gave ethyl 4-(benzoylamino)-3-oxopentanoate (2.6 g, 95.5% yield) as a white solid. ES-MS m/z 263.4 ((MH)+); HPLC RT (min.) 1.53; 1H NMR (Acetone-d6) δ 8.13 (s br, 1H), 7.93-7.91 (m, 2H), 7.58-7.43 (m, 3H), 4.72 (m, 1H), 4.19-4.01 (q, 2H), 3.67 (s, 2H), 1.47 (d, 3H), 1.15 (t, 3H).

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