反応 #46287

反応方程式

sodium bisulfite

potassium hydrogen phosphate

acetic anhydride

ethyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

urea hydrogen peroxide

→

Ethyl 3-(acetyloxy)-6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

溶媒

toluene

dichloromethane

trifluoroacetic anhydride

反応条件

後処理

1. 1
   workup.ADDITIONwas added dropwise over a period of 45 minutes
2. 2
   温度cooled back to 5° C
3. 3
   温度maintained below 25° C
4. 4
   抽出The organic extract
5. 5
   その他was separated
6. 6
   抽出the aqueous fraction extracted with toluene (2×)
7. 7
   乾燥dried over anhydrous sodium sulfate
8. 8
   ろ過filtered
9. 9
   濃縮concentrated under vacuum
10. 10
    その他Without further purification
11. 11
    濃縮The product mixture was concentrated under vacuum
12. 12
    濃縮The resultant oil was concentrated from toluene (300 mL
13. 13
    その他stored under vacuum overnight
14. 14
    その他The acetate product was used in the following step without further purification

実験手順

To a cold (5° C.) mixture of ethyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (199 g, 0.51 mol) and urea hydrogen peroxide (100 g, 1.06 mol) in dichloromethane (1.5 L), trifluoroacetic anhydride was added dropwise over a period of 45 minutes. The resultant homogeneous solution was stirred at 20° C. for 30 minutes and cooled back to 5° C. The reaction mixture was treated with aqueous potassium hydrogen phosphate (pH of aqueous extract increased to ˜8), followed by slow addition of freshly prepared aqueous sodium bisulfite solution with the temperature of the product mixture maintained below 25° C. The organic extract was separated and the aqueous fraction extracted with toluene (2×). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Without further purification, a solution of this intermediate N-oxide (˜280 g) and acetic anhydride (239 mL, 2.5 mol) in toluene (2 L) was heated at 110° C. for 16 hours. The product mixture was concentrated under vacuum. The resultant oil was concentrated from toluene (300 mL, twice) and stored under vacuum overnight. The acetate product was used in the following step without further purification.

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