Reaktion #46281

Reaktionsgleichung

tert-butyl bromoacetate

6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide

magnesium methoxide

→

title compound

Methyl 2-(2-tert-butoxy-2-oxoethyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Lösungsmittel

ethyl acetate

DMSO

methanol

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeMethanol was exhaustively removed under vacuum over 45 minutes
2. 2
   Waschenwashed with ice cold dilute hydrochloric acid
3. 3
   ExtraktionThe organic extract
4. 4
   Waschenwas washed with aqueous sodium thiosulfate, brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under vacuum
8. 8
   SonstigeThe residue was triturated with a mixture of diethyl ether and ethyl acetate
9. 9
   SonstigeThe solid precipitated
10. 10
    Filtrationwas collected by filtration

Vorschrift

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.50 g, 1.31 mmol; Example 1, Step 9) and magnesium methoxide in methanol (6.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (13 mL) was heated at 60° C. for one hour. Methanol was exhaustively removed under vacuum over 45 minutes. The resultant DMSO solution was treated with tert-butyl bromoacetate (1.80 g, 10.50 mmol) and stirred at 50° C. under an atmosphere of nitrogen for one hour. The reaction mixture was diluted with ethyl acetate and washed with ice cold dilute hydrochloric acid. The organic extract was washed with aqueous sodium thiosulfate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was triturated with a mixture of diethyl ether and ethyl acetate. The solid precipitated was collected by filtration to provide the title compound. ES MS M+1=495

Quelle