Réaction #46287

Équation de réaction

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

Solvants

toluene

dichloromethane

trifluoroacetic anhydride

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added dropwise over a period of 45 minutes
2. 2
   Températurecooled back to 5° C
3. 3
   Températuremaintained below 25° C
4. 4
   ExtractionThe organic extract
5. 5
   Autrewas separated
6. 6
   Extractionthe aqueous fraction extracted with toluene (2×)
7. 7
   Séchagedried over anhydrous sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated under vacuum
10. 10
    AutreWithout further purification
11. 11
    ConcentrationThe product mixture was concentrated under vacuum
12. 12
    ConcentrationThe resultant oil was concentrated from toluene (300 mL
13. 13
    Autrestored under vacuum overnight
14. 14
    AutreThe acetate product was used in the following step without further purification

Mode opératoire

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.

Source