Реакция #72436

Уравнение реакции

(S)-4-Benzyloxycarbonylamino-2-hydroxybutyric acid

benzyl bromide

Barium oxide

barium oxide

barium hydroxide octahydrate

→

(S)-2-benzyloxy-4-benzyloxycarbonylaminobutyric acid

Растворители

chloroform

HCl

water

water

acetic acid

N,N-dimethylformamide

chloroform

ethyl acetate

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas added
2. 2
   workup.WAITAfter 5 min
3. 3
   Другоеwas returned to room temperature
4. 4
   workup.WAITAfter 1.5 hr
5. 5
   workup.ADDITIONwas added
6. 6
   workup.ADDITIONwas added
7. 7
   Другоеfollowed by separation
8. 8
   ЭкстракцияThe water layer was extracted with chloroform (50 mL)
9. 9
   Промывкаwere washed with a saturated aqueous NaCl solution
10. 10
    СушкаThe washed solution was dried over magnesium sulfate
11. 11
    ДругоеThe solvent was removed by distillation under the reduced pressure
12. 12
    Другоеthe residue was purified by column chromatography on silica gel (silica gel 60, neutral spheres, 160 g) (chloroform:ethyl acetate=4:1→chloroform:methanol=10:1→chloroform:methanol:acetic acid=10:1:0.1 (600 mL))
13. 13
    Другоеto give (S)-2-benzyloxy-4-benzyloxycarbonylaminobutyrylic acid (2.86 g, 8.34 mmol)

Методика

(S)-4-Benzyloxycarbonylamino-2-hydroxybutyric acid (5.25 g, 20.7 mmol) synthesized according to the report of Kawaguchi et al. (Journal of Antibiotics, Vol. 25, pp. 695-708 (1972)) was dissolved in 60 mL of N,N-dimethylformamide. Barium oxide (15.9 g, 103.7 mmol) was added under an ice bath. After the elapse of 2 min from the addition of barium oxide, barium hydroxide octahydrate (13.4 g, 42.5 mmol) was added thereto under an ice bath. After 10 min, benzyl bromide (7.5 mL, 63.1 mmol) was added thereto under an ice bath. After 5 min, the reaction solution was returned to room temperature and was vigorously stirred. After 1.5 hr, the completion of the reaction was confirmed by TLC (developing solvent system=chloroform:ethyl acetate:acetic acid=10:5:1), and water (0.5 mL) was added thereto under an ice bath. The mixture was diluted with chloroform (165 ml), and 4 N HCl (70 mL) was added thereto. Further, water (25 mL) was added followed by separation. The water layer was extracted with chloroform (50 mL). The organic layer and the extracted organic layer were combined and were washed with a saturated aqueous NaCl solution. The washed solution was dried over magnesium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography on silica gel (silica gel 60, neutral spheres, 160 g) (chloroform:ethyl acetate=4:1→chloroform:methanol=10:1→chloroform:methanol:acetic acid=10:1:0.1 (600 mL)) to give (S)-2-benzyloxy-4-benzyloxycarbonylaminobutyrylic acid (2.86 g, 8.34 mmol).

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