tert-Butyl bromoacetate → 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

HRID 18003

反応式

HRID 18003 の反応式
[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](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].[CH3:28][O-:29].[Mg+2].C[O-].Br[CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>CO.CS(C)=O.C(OCC)(=O)C>[C:38]([O:37][C:35](=[O:36])[CH2:34][N:11]1[C:10](=[O:21])[C:9]([OH:22])=[C:8]2[C:13]([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]2=[O:23])=[C:12]1[C:16]([O:29][CH3:28])=[O:17])([CH3:41])([CH3:40])[CH3:39]

参加物

7

反応物 3

HCID 79177tert-Butyl bromoacetateHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497、化合物

生成物 1

HCID 66997817Methyl 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

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

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

後処理

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. washwashed with ice cold dilute hydrochloric acid
  3. extractionThe organic extract
  4. washwas washed with aqueous sodium thiosulfate, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was triturated with a mixture of diethyl ether and ethyl acetate
  9. customThe solid precipitated
  10. filtrationwas collected by filtration

出典と根拠

ORDレコード
ord-a5504c2c50894d32a7c1fc4dec745e87
出典データセット
uspto-grants-2010_06
特許番号
US07741315B2

関連ノート

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