Tributyltin fluoride → Methyl[5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridin-3-yl]acetate

HRID 1349482노트

반응식

HRID 1349482 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][NH:6][C:7]([C:9]1[N:10]([CH2:25][CH:26]([O:29][CH3:30])[O:27][CH3:28])[CH:11]=[C:12](Br)[C:13](=[O:23])[C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:8].C([Sn](F)(CCCC)CCCC)CCC.[Si]([O:55][CH:56]([O:58][CH3:59])[CH3:57])(C(C)(C)C)(C)C.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:16]([O:15][C:14]1[C:13](=[O:23])[C:12]([CH2:57][C:56]([O:58][CH3:59])=[O:55])=[CH:11][N:10]([CH2:25][CH:26]([O:29][CH3:30])[O:27][CH3:28])[C:9]=1[C:7](=[O:8])[NH:6][CH2:5][C:4]1[CH:31]=[CH:32][CH:33]=[C:2]([Cl:1])[CH:3]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

참가 물질

8

반응물 4

HCID 16120Tributyltin fluorideHCID 516892Sodium BicarbonateHCID 230776861-(Tert-butyldimethylsilyloxy)-1-methoxyethaneHCID 588591313-Benzyloxy-5-bromo-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide

생성물 1

HCID 58859124Methyl[5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridin-3-yl]acetate수율 62.1%

시약·촉매·용매 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)촉매HCID 1140Toluene용매

반응 조건

온도
100 °C

실험 절차

To a solution of 3-benzyloxy-5-bromo-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (300 mg) obtained in Example 161, Step 2 in toluene were added under an argon stream tributyltin fluoride (518 mg), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (58 mg), 1,1′-bis(diphenylphosphino)ferrocene (64 mg) and 1-(tert-butyldimethylsilyloxy)-1-methoxyethane (525 mg), and the mixture was stirred at 100° C. for 15 hr. After cooling to room temperature, aqueous sodium hydrogen carbonate was added to the reaction mixture and the mixture was extracted three times with ethyl acetate. The extract was dried, concentrated and purified by silica gel column chromatography (ethyl acetate) to give methyl [5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridin-3-yl]acetate (184 mg).

후처리

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. customThe extract was dried
  4. concentrationconcentrated
  5. custompurified by silica gel column chromatography (ethyl acetate)

출처 및 근거

ORD 기록
ord-86457739ccdb438694853baaa7b6936c
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07211572B2

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