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

HRID 2066591Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2066591
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:11][CH:10]=[C:9]([O:21][CH3:22])[C:8]=2[C:7]1=[O:23].OO.NC(N)=O.P([O-])([O-])(O)=O.[K+].[K+].S(=O)(O)[O-].[Na+].[C:46]([O:49]C(=O)C)(=[O:48])[CH3:47]>ClCCl.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C1(C)C=CC=CC=1>[C:46]([O:49][C:10]1[N:11]=[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:13]2[CH2:14][CH2:15][N:6]([CH2:5][C:4]3[CH:24]=[CH:25][C:26]([F:27])=[C:2]([Cl:1])[CH:3]=3)[C:7](=[O:23])[C:8]=2[C:9]=1[O:21][CH3:22])(=[O:48])[CH3:47]

Komponenten

9

Edukt 5

HCID 7918Acetic AnhydrideHCID 24450Potassium Phosphate, DibasicHCID 31294Carbamide PeroxideHCID 23665763Sodium BisulfiteHCID 59455605Ethyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Produkt 1

HCID 59455606Ethyl 3-(acetyloxy)-6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 9845Trifluoroacetic anhydrideLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

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.

Aufarbeitung

  1. additionwas added dropwise over a period of 45 minutes
  2. temperaturecooled back to 5° C
  3. temperaturemaintained below 25° C
  4. extractionThe organic extract
  5. customwas separated
  6. extractionthe aqueous fraction extracted with toluene (2×)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customWithout further purification
  11. concentrationThe product mixture was concentrated under vacuum
  12. concentrationThe resultant oil was concentrated from toluene (300 mL
  13. customstored under vacuum overnight
  14. customThe acetate product was used in the following step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-f0e956e9d6ba45a38c92afbc782e443a
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08293731B2

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