Hydrochloric Acid → HCID 59432457、化合物

HRID 2353948ノート

反応式

HRID 2353948 の反応式
COC(=O)[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[C:6]([CH3:11])[C:5]=1[N:12]([CH2:19][CH2:20][CH2:21][C:22]([O:24]CC)=O)[C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14].CC(C)([O-])C.[K+].Cl.[Cl-].[Li+]>C1COCC1.[Cl-].[Na+].O>[CH:16]([O:15][C:13]([N:12]1[CH2:19][CH2:20][CH2:21][C:22](=[O:24])[C:4]2[CH:9]=[CH:8][C:7]([Br:10])=[C:6]([CH3:11])[C:5]1=2)=[O:14])([CH3:17])[CH3:18]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 433294Lithium ChlorideHCID 23665647Potassium tert-butoxideHCID 68681230HCID 68681230、化合物

生成物 1

HCID 59432457HCID 59432457、化合物収率 75.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 57417360Sodium chloride; water溶媒

反応条件

温度
160 °C

実験手順

Add a solution of 2-[(3-Ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-4-bromo-3-methyl-benzoic acid methyl ester (3.47 g, 7.81 mmol) in THF (120 mL) to a solution of potassium tert-butoxide (15.6 mL, 15.62 mmol, 1 M in THF) in THF (120 mL) at room temperature under an atmosphere of nitrogen. After 2 h, pour the mixture into ice/water. Treat aqueous phase with 1M HCl to pH neutral and extract with dichloromethane. Dry the organic layer over anhydrous magnesium sulfate, filter, and remove the solvent under reduced pressure. Dissolve the former crude in DMSO (66 mL) and add water (4 drops) followed by addition of lithium chloride (0.882 g, 20.8 mmol) and heat the resulting solution at 160° C. for 2 h. Cool the mixture to room temperature and pour into brine. Extract the mixture with ethyl acetate. Dry the organic layers over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (2.0 g, 72% over two steps): MS (ES+): 341 (M+H).

後処理

  1. extractionextract with dichloromethane
  2. dry with materialDry the organic layer over anhydrous magnesium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. dissolutionDissolve the former crude in DMSO (66 mL)
  6. additionadd water (4 drops)
  7. temperatureCool the mixture to room temperature
  8. extractionExtract the mixture with ethyl acetate
  9. dry with materialDry the organic layers over anhydrous magnesium sulfate
  10. filtrationfilter
  11. customremove the solvent under reduced pressure
  12. customPurify the residue by flash chromatography
  13. washeluting with hexanes/ethyl acetate

出典と根拠

ORDレコード
ord-2023753102d1406da7e058c2b614f6ce
出典データセット
uspto-grants-2010_07
特許番号
US07749992B2

反応ノート

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