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Sodium Iodide → 4-[2',4'-Dichloro-3'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-butyric acid

HRID 2235284
ノート
印刷プレビュー

反応式

HRID 2235284 の反応式
[CH:1]1([N:7]2[CH2:11][CH2:10][CH:9]([CH2:12][C:13]3[C:14]([Cl:27])=[C:15]([C:20]4[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=4)[CH:16]=[CH:17][C:18]=3[Cl:19])[C:8]2=[O:28])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[I-].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:38][CH2:39][CH2:40][C:41]([O:43]C(C)(C)C)=[O:42]>C1COCC1>[Cl:27][C:14]1[C:13]([CH2:12][CH:9]2[CH2:10][CH2:11][N:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[C:8]2=[O:28])=[C:18]([Cl:19])[CH:17]=[CH:16][C:15]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[CH:22][CH:21]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 2757253tert-Butyl 4-bromobutanoateHCID 592993283-(3-(4-Hydroxyphenyl)-2,6-dichlorobenzyl)-1-cyclohexylpyrrolidin-2-one

生成物 1

HCID 592994774-[2',4'-Dichloro-3'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-butyric acid収率 66%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Place 1-cyclohexyl-3-(2,4-dichloro-4′-hydroxy-biphenyl-3-ylmethyl)-pyrrolidin-2-one (Example 113) (200 mg, 0.5 mmol), sodium iodide (72 mg, 0.5 mmol), and cesium carbonate (1.25 g, 3.8 mmol) in THF (10 mL). Add tert-butyl 4-bromobutanoate (213 mg, 1.0 mmol) and stir at room temperature for 3 hours. Add dichloromethane and wash with water. Dry over sodium sulfate, filter, and concentrate. Dissolve residue in dichloromethane (5 mL) and TFA (5 mL) and stir for 30 minutes. Remove solvent and dissolve product in IM NaOH. The deprotonated carboxylic acid does not go into the aqueous layer. Bring the pH ˜2 with 6M HCl and extract with dichloromethane. Dry over sodium sulfate, filter, and concentrate. Purify by silica gel (dichloromethane-5% methanol in dichloromethane) affords 158 mg (66%) the title compound as a brown solid: Mass spectrum (apci) m/z=504.2 (M+H).

後処理

  1. washAdd dichloromethane and wash with water
  2. dry with materialDry over sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate
  5. dissolutionRemove solvent and dissolve product in IM NaOH
  6. extractionBring the pH ˜2 with 6M HCl and extract with dichloromethane
  7. dry with materialDry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify by silica gel (dichloromethane-5% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-fbd7fd4b9ac64fbabde67780d8f8566e
出典データセット
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07713979B2

反応ノート

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