Reaktion #46287

Reaktionsgleichung

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

Lösungsmittel

toluene

dichloromethane

trifluoroacetic anhydride

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise over a period of 45 minutes
2. 2
   Temperaturcooled back to 5° C
3. 3
   Temperaturmaintained below 25° C
4. 4
   ExtraktionThe organic extract
5. 5
   Sonstigewas separated
6. 6
   Extraktionthe aqueous fraction extracted with toluene (2×)
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated under vacuum
10. 10
    SonstigeWithout further purification
11. 11
    EinengenThe product mixture was concentrated under vacuum
12. 12
    EinengenThe resultant oil was concentrated from toluene (300 mL
13. 13
    Sonstigestored under vacuum overnight
14. 14
    SonstigeThe acetate product was used in the following step without further purification

Vorschrift

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.

Quelle