Ethyl Acetate → Ethyl 4-benzamido-3-oxopentanoate

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).

1. temperaturecooled down to −78° C
2. additionwas added
3. stirringThe resulting solution was stirred 30 minutes at −78° C.
4. stirringThe resulting white slurry was stirred 30 minutes at −78° C.
5. temperaturewarmed up to −10° C
6. customThe reaction was quenched with a saturated aqueous solution of NH4Cl
7. customPhases were separated
8. dry with materialthe organics were dried over MgSO4 and solvents
9. customremoved under reduced pressure
10. customThe crude product was carried to the next step without purification

ORD record

ord-49c296ddbcb94d80a0d258dfb8b44ec5

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07112597B2