Sodium hydride → 1-(1-benzhydryl-azetidin-3-ylmethyl)-6-fluoro-1H-indole

HRID 28485ノート

反応式

HRID 28485 の反応式
[H-].[Na+].[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1.[CH:13]([N:26]1[CH2:29][CH:28]([CH2:30]OS(C)(=O)=O)[CH2:27]1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C=O)C>[CH:13]([N:26]1[CH2:29][CH:28]([CH2:30][N:10]2[C:11]3[C:7](=[CH:6][CH:5]=[C:4]([F:3])[CH:12]=3)[CH:8]=[CH:9]2)[CH2:27]1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 3512786-FluoroindoleHCID 21978370(1-Benzhydrylazetidin-3-yl)methyl methanesulfonate

生成物 1

HCID 692042621-(1-benzhydryl-azetidin-3-ylmethyl)-6-fluoro-1H-indole収率 70.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

To a suspension of sodium hydride (60% mineral oil dispersion, 0.19 g, 4.6 mmol) in anhydrous DMF (20 mL) was added 6-fluoroindole (0.65. g, 2.6 mmol) at 0° C. The mixture was stirred at 0° C. for 30 minutes, then a solution of methanesulfonic acid 1-benzhydryl-azetidine-3-ylmethyl ester (0.78 g, 2.3 mmol) in DMF was introduced at 0° C. The resulting mixture heated at 60° C. for 16 hours. The reaction was quenched with water and extracted with methylene chloride (3×50 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum. The crude oil was column chromatographed on silica gel (10-30% ethyl acetate-hexane). The product-containing fractions were concentrated under vacuum to give 0.60 g (52%) of the title compound as a light brown oil. MS ES m/e 371 (M+H)+; 1H NMR (500 MHz, DMSO-D6): 2.76-2.79 δ (m, 3H), 3.05-3.07 δ (m, 2H), 4.29-4.31 δ (m, 3H), 6.37 δ (m, 1H), 6.78-6.83 δ (m, 1H), 7.09-7.13 δ (m, 2H), 7.18-7.22 δ (m, 4H), 7.31-7.35 δ (m, 6H), 7.46 δ (m, 1H).

後処理

  1. temperatureThe resulting mixture heated at 60° C. for 16 hours
  2. customThe reaction was quenched with water
  3. extractionextracted with methylene chloride (3×50 mL)
  4. washThe organic layer was washed with water (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under vacuum
  8. customchromatographed on silica gel (10-30% ethyl acetate-hexane)
  9. concentrationThe product-containing fractions were concentrated under vacuum

出典と根拠

ORDレコード
ord-2b3c80d340034ebbb9deaed1cfe09201
出典データセット
uspto-grants-2008_09
特許番号
US07419986B2

反応ノート

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