Hydrochloric Acid → 2-(2-{4-[1-(4-fluoro-benzyl)-1H-indol-3-yl]-piperidin-1-yl}-ethoxy)-benzoic acid

HRID 1840935ノート

反応式

HRID 1840935 の反応式
[H-].[Na+].C[O:4][C:5](=[O:30])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][CH:22]=2)[CH2:17][CH2:16]1.[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][CH:33]=1.Cl>CN(C=O)C>[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][N:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:21]([CH:18]3[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][O:12][C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=4[C:5]([OH:4])=[O:30])[CH2:16][CH2:17]3)=[CH:22]2)=[CH:34][CH:33]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 11440344methyl 2-{2-[4-(1H-indol-3-yl)-piperidin-1-yl]-ethoxy}-benzoate

生成物 1

HCID 98476332-(2-{4-[1-(4-fluoro-benzyl)-1H-indol-3-yl]-piperidin-1-yl}-ethoxy)-benzoic acid収率 84%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

0.02 g (0.42 mmol) of a dispersion of 60% NaH in mineral oil were added to a solution of 0.06 g (0.15 mmol) of 2-{2-[4-(1H-indol-3-yl)-piperidin-1-yl]-ethoxy}-benzoic acid methyl ester prepared in step D in 1 mL of anhydrous DMF under nitrogen atmosphere. After stirring 30 minutes at room temperature 0.026 mL (0.21 mmol) of 4-fluoro-benzyl bromide were added and the mixture was stirred for 18 hours. After addition of 0.09 g (0.12 mmol) of 3-(3-mercapto-phenyl)-propanamido-methyl-polystyrene in 1 mL of DMF the mixture was stirred overnight at room temperature. 0.1 mL of 2N HCl were added to the reaction mixture and the crude-was filtered. The solvent was removed under reduced pressure and the crude mixture was purified using a 500 mg Varian C18 chromatography column affording 0.059 g (84% yield) of 2-(2-{4-[1-(4-fluoro-benzyl)-1H-indol-3-yl]-piperidin-1-yl}-ethoxy)-benzoic acid.

後処理

  1. additionwere added
  2. stirringwas stirred overnight at room temperature
  3. filtrationthe crude-was filtered
  4. customThe solvent was removed under reduced pressure
  5. customthe crude mixture was purified

出典と根拠

ORDレコード
ord-74e3a4d7fc9f401dbb9670558390d002
出典データセット
uspto-grants-2004_01
特許番号
US06683096B2

反応ノート

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