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

HRID 1884670노트

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HRID 1884670 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-6b71a0aad4704d5aac0c30a7a795c525
출처 데이터셋
uspto-grants-2004_07
특허 번호
US06765021B2

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