Реакция #46281

Уравнение реакции

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

Растворители

ethyl acetate

DMSO

methanol

DMSO

Условия реакции

Обработка

1. 1
   ДругоеMethanol was exhaustively removed under vacuum over 45 minutes
2. 2
   Промывкаwashed with ice cold dilute hydrochloric acid
3. 3
   ЭкстракцияThe organic extract
4. 4
   Промывкаwas washed with aqueous sodium thiosulfate, brine
5. 5
   Сушкаdried over anhydrous sodium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated under vacuum
8. 8
   ДругоеThe residue was triturated with a mixture of diethyl ether and ethyl acetate
9. 9
   ДругоеThe solid precipitated
10. 10
    Фильтрацияwas collected by filtration

Методика

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

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