Citric Acid → Methyl 3-(4-bromophenyl)-2,2-dimethylpropanoate

HRID 1107501ノート

反応式

HRID 1107501 の反応式
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:18][CH3:19])(=[O:17])[CH:14]([CH3:16])[CH3:15].[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCCCCC.O1CCCC1>[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][C:14]([C:13]([O:18][CH3:19])=[O:17])([CH3:16])[CH3:15])=[CH:23][CH:22]=1

参加物

8

反応物 5

HCID 311Citric AcidHCID 7912DiisopropylamineHCID 11039Methyl isobutyrateHCID 685274-Bromobenzyl bromideHCID 178418339Butyllithium

生成物 1

HCID 22503289Methyl 3-(4-bromophenyl)-2,2-dimethylpropanoate収率 71.9%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
-70 °C

実験手順

A 1.25M solution of n-butyl lithium in hexane (32 ml) was cooled to 0° C. under an argon atmosphere and diisopropylamine (4.05 g; 5.24 ml) was added slowly. The resulting mixture was cooled to -70° C. and stirred while methyl isobutyrate (4.08 g; 4.58 ml) was added dropwise while maintaining the temperature at <-60° C. After a further 30 minutes at -70° C., a solution of 4-bromobenzyl bromide (10.0 g) in anhydrous tetrahydrofuran (20 ml) was added and the temperature was maintained at -70° C. for further 1.5 hours. The reaction mixture was allowed to attain ambient temperature then heated to reflux for 18 hours. On cooling, the mixture was acidified with 8% aqueous citric acid and extracted with ethyl acetate (3×75 ml). Insoluble material at the interface was removed by filtration and the combined organic phase was washed with brine (20 ml), dried (Mg SO4) and evaporated. The residue was purified by vacuum flash chromatography on silica eluting with a gradient of 0-10% ethyl acetate in hexane to give 1-bromo-4-(2-methoxycarbonyl-2-methylpropyl)benzene (7.79 g); 1H NMR (d6 -DMSO): 1.13 (s, 6H); 2.79 (s, 2H), 3.60 (s, 3H), 7.04 (m, 2H), 7.46 (d of t, 2H); mass spectrum (CI+): 272 (M+H)+.

後処理

  1. additionwas added dropwise
  2. temperaturewhile maintaining the temperature at <-60° C
  3. temperaturethe temperature was maintained at -70° C. for further 1.5 hours
  4. customto attain ambient temperature
  5. temperaturethen heated
  6. temperatureto reflux for 18 hours
  7. temperatureOn cooling
  8. extractionextracted with ethyl acetate (3×75 ml)
  9. customInsoluble material at the interface was removed by filtration
  10. washthe combined organic phase was washed with brine (20 ml)
  11. dry with materialdried (Mg SO4)
  12. customevaporated
  13. customThe residue was purified by vacuum flash chromatography on silica eluting with a gradient of 0-10% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-d0f3b408dcb9466fa1f5519e1ab169d7
出典データセット
uspto-grants-2000_05
特許番号
US06060475

反応ノート

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