5-Fluoro-1-(phenylsulfonyl)-1H-indole → 4-[(1-benzenesulfonyl-5-fluoro-1H-indol-2-yl)-hydroxy-methyl]4-propyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1895043ノート

反応式

HRID 1895043 の反応式
[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]C(C)(C)C.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([CH:41]=[O:42])([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([CH:41]([C:11]2[N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:9])=[O:8])[C:18]3[C:13]([CH:12]=2)=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[OH:42])([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:33]1)=[O:31])([CH3:27])([CH3:28])[CH3:26]

参加物

5

反応物 3

HCID 112888585-Fluoro-1-(phenylsulfonyl)-1H-indoleHCID 58017246Tert-butyl 4-formyl-4-propylpiperidine-1-carboxylateHCID 178418306HCID 178418306、化合物

生成物 1

HCID 666875264-[(1-benzenesulfonyl-5-fluoro-1H-indol-2-yl)-hydroxy-methyl]4-propyl-piperidine-1-carboxylic acid tert-butyl ester収率 53%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-20 °C

実験手順

To a −78° C. solution of 1-benzenesulfonyl-5-fluoro-1H-indole (539 mg, 1.96 mmol) in 30 mL THF, t-BuLi (1.5 mL, 2.54 mmol) was slowly added. The reaction mixture was stirred for 30 minutes, then a solution of 4-formyl-4-propyl-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.96 mmol) in 5 mL THF was added. The reaction was allowed to stir for 2 hours at −78° C. and was then warmed to −20° C. and quenched with a saturated aqueous solution of ammonium chloride. The reaction mixture was extracted with ethyl acetate and the combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated onto silica. The material was chromatographed over a 25 g Thomson column eluting with 20% ethyl acetate 80% hexanes to afford 4-[(1-benzenesulfonyl-5-fluoro-1H-indol-2-yl)-hydroxy-methyl]-4-propyl-piperidine-1-carboxylic acid tert-butyl ester (319 mg, 0.6 mmol) in a 53% yield as a beige foam.

後処理

  1. stirringto stir for 2 hours at −78° C.
  2. customquenched with a saturated aqueous solution of ammonium chloride
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated onto silica
  8. customThe material was chromatographed over a 25 g Thomson column
  9. washeluting with 20% ethyl acetate 80% hexanes

出典と根拠

ORDレコード
ord-8319c0a4013446e5bfd9b7f0f4dba780
出典データセット
uspto-grants-2013_08
特許番号
US08513425B2

反応ノート

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