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Hydrochloric Acid → 6-Oxo-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester

HRID 2353938
ノート
印刷プレビュー

反応式

HRID 2353938 の反応式
COC([C:5]1[C:6]([N:14]([CH2:21][CH2:22][CH2:23][C:24](OCC)=[O:25])[C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH2:9][CH2:8]2)=O.CC(C)([O-])C.[K+].Cl.[Cl-].[Li+]>C1COCC1.[Cl-].[Na+].O>[CH:18]([O:17][C:15]([N:14]1[C:6]2[C:7]3[CH2:8][CH2:9][CH2:10][C:11]=3[CH:12]=[CH:13][C:5]=2[C:24](=[O:25])[CH2:23][CH2:22][CH2:21]1)=[O:16])([CH3:19])[CH3:20]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 433294Lithium ChlorideHCID 23665647Potassium tert-butoxideHCID 593791374-[(3-Ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-indan-5-carboxylic acid methyl ester

生成物 1

HCID 593791336-Oxo-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester収率 81%

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 4-[(3-Ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-indan-5-carboxylic acid methyl ester (510 mg, 1.30 mmol) in THF (20.4 mL) to a solution of potassium tert-butoxide (2.60 μL, 2.60 mmol, 1 M in THF) in THF (18 mL) at room temperature under an atmosphere of nitrogen. After 30 min, 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 sodium sulfate, filter, and remove the solvent under reduced pressure. Dissolve the former crude in DMSO (11 mL) and add water (2 drops) followed by addition of lithium chloride (134 mg, 3.2 mmol) and heat the resulting solution at 160° C. for 30 minutes. Cool the mixture to room temperature and pour into brine. Extract the mixture with ethyl acetate. Dry the organic layers over anhydrous sodium 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 (302 mg, 81% over two steps): MS (ES+): 288 (M+H).

後処理

  1. extractionextract with dichloromethane
  2. dry with materialDry the organic layer over anhydrous sodium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. dissolutionDissolve the former crude in DMSO (11 mL)
  6. additionadd water (2 drops)
  7. temperatureCool the mixture to room temperature
  8. extractionExtract the mixture with ethyl acetate
  9. dry with materialDry the organic layers over anhydrous sodium 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-4550f0fc118246ac98e067f7b3146f05
出典データセット
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07749992B2

反応ノート

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