Sodium hydride → {2-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1':3',1'']terphenyl-2'-yloxy]-ethoxy}acetic acid, methyl ester

HRID 1281432

反応式

HRID 1281432 の反応式
[N:1]1([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:44])[C:20]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:23]([O:33][CH2:34][CH2:35][OH:36])=[C:22]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=3)[CH:21]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[CH3:47][O:48][C:49](=[O:52])[CH2:50]Br.C1OCCOCCOCCOCCOC1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:32][C:28]1[CH:27]=[C:26]([C:24]2[CH:25]=[C:20]([C:19](=[O:44])[NH:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][N:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH:3]=[CH:2]3)[CH:21]=[C:22]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=3)[C:23]=2[O:33][CH2:34][CH2:35][O:36][CH2:50][C:49]([O:48][CH3:47])=[O:52])[CH:31]=[CH:30][CH:29]=1

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 60984Methyl bromoacetateHCID 22237401N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)-4-(2-hydroxyethoxy)benzamide

生成物 1

HCID 86583669{2-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1':3',1'']terphenyl-2'-yloxy]-ethoxy}acetic acid, methyl ester

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)-4-(2-hydroxyethoxy)benzamide (0.629 g, 1 mmol) in THF (10 ml) under nitrogen at room temperature was sodium hydride (0.055 g, 2.3 mmol). The mixture was refluxed for 45 minutes, cooled and methylbromoacetate (0.189 g, 1.2 mmol), 15-crown-5 ether (0.022 g, 0.1 mmol), and tetrabutylammoniumiodide (0.037 g, 0.1 mmol) were added. The mixture was refluxed. After 6 h, the reaction mixture was quenched with water and then diluted with water (100 ml) and extracted with EtOAc. This gave a thick emulsion which was separated by acidfying the mixture with 1N HCl. The combined extracts were washed with water (2×15 ml), brine (2×15 ml), dried over Na2SO4, filtered and the filtrate concentrated in vac and dried. The residue was purified by flash chromatography (15%, 20% EtOAc/Hex) and then preparatory plate chromatography (50% EtOAc/Hex) to give the desired product as a viscous, hazy oil (0.400 g, 57%); 1H NMR (400 MHz, DMSO-d6) δ 1.16-1.31 (m, 8H), 1.45-1.53 (m, 2H), 1.68-1.76 (m, 2H), 3.20-3.26 (m, 4H), 3.45-3.48 (m, 2H), 3.58 (s, 3H), 3.71 (s, 2H), 4.12 (t, J=6.8 Hz, 2H), 6.37 (dd, J=0.8, 3.1 Hz, 1H), 6.95-6.99 (m, 1H), 7.06-7.10 (m, 1H), 7.32 (d, J=3.1 Hz, 1H), 7.40-7.52 (m, 6H), 7.57-7.60 (m, 2H), 7.67-7.70 (m, 2H), 7.87 (s, 2H), 8.52 (t, J=4.83 Hz, 1H); IR (film) 3300, 2800, 1750, 1630, 1540, 1470, 1220 cm−1; mass spectrum [(+)APCI], m/z 701 (M+H)+.

後処理

  1. customat room temperature
  2. temperatureThe mixture was refluxed for 45 minutes
  3. temperaturecooled
  4. temperatureThe mixture was refluxed
  5. customthe reaction mixture was quenched with water
  6. additiondiluted with water (100 ml)
  7. extractionextracted with EtOAc
  8. customThis gave a thick emulsion which
  9. customwas separated
  10. washThe combined extracts were washed with water (2×15 ml), brine (2×15 ml)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationthe filtrate concentrated in vac
  14. customdried
  15. customThe residue was purified by flash chromatography (15%, 20% EtOAc/Hex)

出典と根拠

ORDレコード
ord-e2df7af7bf914926b73c8c611369331a
出典データセット
uspto-grants-2002_09
特許番号
US06451827B2

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