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

반응식

HRID 18003 반응식
[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]

참가 물질

7

반응물 3

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

생성물 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

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매2회HCID 887Methanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-a5504c2c50894d32a7c1fc4dec745e87
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741315B2

연결된 노트

불러오는 중…