반응 #216278

반응 방정식

Trimethyl orthoacetate

inosine

sodium carbonate

NaOH

acetyl bromide

NaOH

hydrogen

→

2',3'-dideoxyinosine

수율 45.9%

용매

acetonitrile

acetonitrile

acetic acid

반응 조건

후처리

1. 1
   농축The reaction solution was concentrated to 26.7 g
2. 2
   workup.ADDITIONwas slowly added to the mixture
3. 3
   workup.STIRRINGwith stirring
4. 4
   기타at -5° C. to 0° C
5. 5
   workup.ADDITIONAfter completion of the addition
6. 6
   workup.STIRRINGthe mixture was stirred at -5° C. to 0° C. for about an hour
7. 7
   workup.ADDITIONwere added to the neutralized reaction solution, pH
8. 8
   workup.WAITwas passed at 7° to 8° C. in a flow amount of 30 ml/min for 10 hours
9. 9
   온도During the procedure, the pH was maintained between 8.0 and 8.5
10. 10
    여과Palladium carbon was filtered off
11. 11
    농축The filtrate was concentrated under reduced pressure and acetonitrile
12. 12
    workup.DISTILLATIONwas distilled off
13. 13
    workup.ADDITIONAfter about 25 ml of 25% NaOH was added to the residue
14. 14
    workup.STIRRINGthe mixture was stirred at 50° C. for 30 minutes

실험 절차

Trimethyl orthoacetate (6.49 ml, 51.0 mmols) was added to 10 g (37.2 mmols of inosine suspended in 20 ml of acetic acid. The mixture was stirred at 25° C. for 10 hours. The reaction solution was concentrated to 26.7 g. After 35 ml of acetonitrile was added to the concentrate, 6.9 ml (93.4 mmols) of acetyl bromide was slowly added to the mixture with stirring while keeping the temperature at -5° C. to 0° C. After completion of the addition, the mixture was stirred at -5° C. to 0° C. for about an hour. The reaction solution was neutralized with 20% sodium carbonate aqueous solution. A small amount of the solution was taken out and analyzed by HPLC. The desired Br--AcO--Hx was contained in 10.9 g (70.6% yield based on inosine). After 15 ml of acetonitrile and 2.1 g of 10% palladium carbon were added were added to the neutralized reaction solution, pH was adjusted to 8.5 with 25% NaOH and hydrogen gas was passed at 7° to 8° C. in a flow amount of 30 ml/min for 10 hours. During the procedure, the pH was maintained between 8.0 and 8.5, using 25% NaOH. Palladium carbon was filtered off. The filtrate was concentrated under reduced pressure and acetonitrile was distilled off. After about 25 ml of 25% NaOH was added to the residue, the mixture was stirred at 50° C. for 30 minutes to give 4.03 g (yield of 45.9% based on inosine) of 2',3'-dideoxyinosine A 300 MHz nuclear magnetic resonance absorption spectrum of the isolated 2',3'-dideoxyinosine supported the structure of this product.

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