Dimethyl malonate → 2-[4-bromo-5-chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-malonic acid dimethyl ester

HRID 2382709ノート

反応式

HRID 2382709 の反応式
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[Br:12][C:13]1[C:14]([Cl:35])=[CH:15][C:16](F)=[C:17]([S:19]([N:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]([CH3:33])([CH3:32])[CH2:24][CH2:23]2)(=[O:21])=[O:20])[CH:18]=1>CN(C=O)C>[CH3:6][O:5][C:3](=[O:4])[CH:2]([C:16]1[CH:15]=[C:14]([Cl:35])[C:13]([Br:12])=[CH:18][C:17]=1[S:19]([N:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([CH3:33])([CH3:32])[CH2:24][CH2:23]1)(=[O:21])=[O:20])[C:1]([O:8][CH3:9])=[O:7]

参加物

5

反応物 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 684692731-(5-Bromo-4-chloro-2-fluoro-benzenesulfonyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline

生成物 1

HCID 684691712-[4-bromo-5-chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-malonic acid dimethyl ester収率 59.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
80 °C

実験手順

To a dry DMF (10 mL) solution containing dimethyl malonate (0.79 mL, 6.9 mmol), was added NaH (276 mg, 6.9 mmol) slowly at 0° C. under N2. The slurry was stirred for 10 min, then 1-(5-bromo-4-chloro-2-fluoro-benzenesulfonyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline (1.0 g, 2.3 mmol) in dry DMF (5 mL) was added dropwise. The mixture was heated at 80° C. for 24 hrs, cooled to rt, carefully quenched with 1N HCl (10 mL), and extracted with ethyl acetate. The organic layer was washed with saturated aq. NaHCO3 solution and water, then was dried over MgSO4. After filtration and concentration, the residue was purified via silica gel flash column chromatography eluting with hexane/ethyl acetate (100/15) to yield 2-[4-bromo-5-chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-malonic acid dimethyl ester (0.75 g). MS: 545.9 (M+H)+; tR=2.64 min (method 1)

後処理

  1. temperaturecooled to rt
  2. customcarefully quenched with 1N HCl (10 mL)
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated aq. NaHCO3 solution and water
  5. dry with materialwas dried over MgSO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified via silica gel flash column chromatography
  8. washeluting with hexane/ethyl acetate (100/15)

出典と根拠

ORDレコード
ord-3fd604567a6543a4a5b50510f3a14e8b
出典データセット
uspto-grants-2012_09
特許番号
US08263588B2

反応ノート

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