Réaction #46281

Équation de réaction

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

Solvants

ethyl acetate

DMSO

methanol

DMSO

Conditions de réaction

Traitement

1. 1
   AutreMethanol was exhaustively removed under vacuum over 45 minutes
2. 2
   Lavagewashed with ice cold dilute hydrochloric acid
3. 3
   ExtractionThe organic extract
4. 4
   Lavagewas washed with aqueous sodium thiosulfate, brine
5. 5
   Séchagedried over anhydrous sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under vacuum
8. 8
   AutreThe residue was triturated with a mixture of diethyl ether and ethyl acetate
9. 9
   AutreThe solid precipitated
10. 10
    Filtrationwas collected by filtration

Mode opératoire

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

Source