تفاعل #348057

معادلة التفاعل

sodium hypochlorite

sodium bicarbonate

sodium hypochlorite

sodium bromide

sodium thiosulfate pentahydrate

N-Carboxybenzyl-D-phenylalaninol

→

N-carboxybenzyl-D-phenylalaninal

المردود 90.6%

المذيبات

water

water

dichloromethane

water

ethyl acetate toluene

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled to 0°-5° C. under a nitrogen atmosphere
2. 2
   workup.ADDITION2,2,6,6-Tetramethyl-1-piperidinyloxy free radical (TEMPO) (0.055-0.55 g; 3.5-35 mM) is added
3. 3
   workup.ADDITIONis added over a period of one hour with fast agitation
4. 4
   درجة الحرارةmaintaining the reaction temperature <5° C
5. 5
   workup.STIRRINGthe reaction mixture efficiently stirred until excess oxidants
6. 6
   أخرىhave been quenched
7. 7
   أخرىto settle at 5°-10° C
8. 8
   أخرىthe phases are separated
9. 9
   غسيلThe organic phase is then washed with aqueous sodium bicarbonate solution (3% w/w; 500 mL) and aqueous sodium chloride solution (3% w/w; 500 mL)
10. 10
    تركيزThe organic phase is concentrated by vacuum distillation to a volume of approximately 300 mL
11. 11
    درجة الحرارةmaintaining the heating bath <20° C
12. 12
    workup.ADDITIONHeptane (750 mL) is added
13. 13
    workup.DISTILLATIONthe vacuum distillation
14. 14
    أخرىto precipitate the product
15. 15
    درجة الحرارةwhile maintaining the heating bath <20° C
16. 16
    ترشيحThe precipitate is filtered
17. 17
    غسيلwashed with heptane (2×200 mL)
18. 18
    أخرىdried under vacuum at 20° C. to constant weight

الإجراء التجريبي

N-Carboxybenzyl-D-phenylalaninol (100 g ;0.35M) is dissolved in ethyl acetate/toluene (1:1; 1.5-2.0 L) or dichloromethane (1.0-2.0 L) and a solution of sodium bromide (18.0-25.2 g; 0.175-0.25M) in water (50-250 mL) added. The resulting two phase mixture is stirred and cooled to 0°-5° C. under a nitrogen atmosphere. 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical (TEMPO) (0.055-0.55 g; 3.5-35 mM) is added. A solution of buffered sodium hypochlorite, freshly prepared by dissolving sodium bicarbonate (10-25 g; 0.12-0.3M) and commercial sodium hypochlorite solution (6-12.5% w/w; 250-584 g; 0.42-0.49M) in water (25-250 g), is added over a period of one hour with fast agitation, maintaining the reaction temperature <5° C. A solution of sodium thiosulfate pentahydrate (21.8-122 g; 0.088-0.49M) in water (64 -370 mL) is then immediately added and the reaction mixture efficiently stirred until excess oxidants have been quenched as demonstrated by starch/iodide test. Agitation is stopped and the mixture allowed to settle at 5°-10° C. After 15 minutes, the phases are separated. The organic phase is then washed with aqueous sodium bicarbonate solution (3% w/w; 500 mL) and aqueous sodium chloride solution (3% w/w; 500 mL). The organic phase is concentrated by vacuum distillation to a volume of approximately 300 mL maintaining the heating bath <20° C. Heptane (750 mL) is added and the vacuum distillation optionally continued to precipitate the product, while maintaining the heating bath <20° C. The precipitate is filtered, washed with heptane (2×200 mL) and dried under vacuum at 20° C. to constant weight to yield N-carboxybenzyl-D-phenylalaninal (90 g; 90% yield) as a white crystalline solid.

المصدر