8-Phenyloctan-1-amine → N-(8-Phenyl-octyl)-3,5-bis-(m-chlorophenyl)4-(2-hydroxyethoxy)-benzamide

HRID 1884670ノート

反応式

HRID 1884670 の反応式
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.C([O:23][C:24](=O)[C:25]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=2)[C:28]([O:38][CH2:39][CH2:40][OH:41])=[C:27]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[CH:43]=2)[CH:26]=1)C>C1COCC1>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:24](=[O:23])[C:25]2[CH:26]=[C:27]([C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[CH:43]=3)[C:28]([O:38][CH2:39][CH2:40][OH:41])=[C:29]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=3)[CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

参加物

5

反応物 3

HCID 1455568-Phenyloctan-1-amineHCID 539906423,5-Bis-(m-chlorophenyl)4-(2-hydroxyethoxy)benzoic acid ethyl esterHCID 178418339Butyllithium

生成物 1

HCID 22237408N-(8-Phenyl-octyl)-3,5-bis-(m-chlorophenyl)4-(2-hydroxyethoxy)-benzamide収率 65%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a flamed dried round bottom flask with 8-phenyloctyl amine (0.484 mL, 2.43 mmol) and THF (5 mL) cooled to 0° C. was added n-BuLi (0.972 mL, 2.5 M in hexane, 2.43 mmol) dropwise over a 5 min. period. The resulting solution was allowed to stir 5 min. and then warmed to room temperature for 30 min. This solution was then added dropwise to a solution of 3,5-bis-(m-chlorophenyl)-4-(2-hydroxyethoxy)benzoic acid ethyl ester (0.300 g, 0.696 mmol) in THF (15 mL) at −20° C. This final mixture was stirred at −20° C. for 15 min and then warmed to room temperature for 15 min. At this point, the reaction mixture was quenched with H2O (10 mL) and diluted with EtOAc (200 mL). The organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 (20 to 40% EtOAc/petroleum ether gradient) to afford the product (0.267 g, 65%) as a clear oil; 1H NMR (400 MHz, CDCl3) δ 1.09-1.48 (m, 9H), 1.48-1.72 (m, 4H), 2.58 (t, J=6.8 Hz, 2H), 3.30-3.35 (m, 2H), 3.35-3.41 (m, 2H), 3.46 (dd, J=6.8, 13.0 Hz, 2H), 6.07-6.18 (m, 1H), 7.11-7.19 (m, 3H), 7.21-7.31 (m, 2H), 7.35-7.44 (m, 4H), 7.44-7.57 (m, 2H), 7.63 (s, 2H), 7.77 (s, 2H); mass spectrum [(+) ESI], m/z 590 (M)+.

後処理

  1. temperaturewarmed to room temperature for 30 min
  2. temperaturewarmed to room temperature for 15 min
  3. customAt this point, the reaction mixture was quenched with H2O (10 mL)
  4. additiondiluted with EtOAc (200 mL)
  5. washThe organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationAfter concentration
  8. customthe residue was purified by the Biotage Flash 40 (20 to 40% EtOAc/petroleum ether gradient)

出典と根拠

ORDレコード
ord-6b71a0aad4704d5aac0c30a7a795c525
出典データセット
uspto-grants-2004_07
特許番号
US06765021B2

反応ノート

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