Sodium hydride → {[1-Bromo-6-(1-methyl-3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetic acid

HRID 1866480노트

반응식

HRID 1866480 반응식
C[O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:16]3[NH:17][C:18]4[C:23]([C:24]=3[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:12]=2)[C:7]=1[Br:30].[CH3:32]C([O-])(C)C.[K+].[H-].[Na+]>C1COCC1>[Br:30][C:7]1[C:8]2[C:13](=[CH:12][C:11]([C:16]3[N:17]([CH3:32])[C:18]4[C:23]([C:24]=3[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:10][CH:9]=2)[CH:14]=[CH:15][C:6]=1[O:5][CH2:4][C:3]([OH:2])=[O:31]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 23665647Potassium tert-butoxideHCID 57453746{[1-Bromo-6-(3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetic acid methyl ester

생성물 1

HCID 10140643{[1-Bromo-6-(1-methyl-3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetic acid수율 57%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred solution of {[1-bromo-6-(3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetic acid methyl ester (0.410 g, 0.853 mmol) in THF (20 mL) at 0° C. was added KOt-Bu (0.105 g, 0.938 mmol) followed by Mel (0.064 mL, 1.02 mmol). The reaction was warmed to rt and let stir for 1 h. It appeared by TLC and MS that all the starting material was gone; however, two polar acids (one N—Me and one N—H) had been generated due to hydrolysis in these basic conditions. After concentration, the residue was taken up in DMF (20 mL). Added NaH (0.075 g, 60% by wt., 1.88 mmol) followed by excess Mel to convert all intermediate to one acid (N—Me). After 1 h, the reaction mixture was concentrated and then diluted with EtOAc (200 mL) and 1 N HCl (20 mL). The organic layer was washed with H2O (20 mL) and brine (20 mL) and then dried (Na2SO4). After concentration, the residue was purified by preparatory plate chromatography (10% MeOH:CHCl3) to afford the product (0.232 g, 57%) as a yellowish-orange foamy solid, mp>73° C. (decomp.); 1H NMR (DMSO-d6) δ 0.73 (t, J=7.0 Hz, 3H), 1.11-1.20 (m, 4H), 1.50-1.58 (m, 2H), 2.66 (t, J=7.3 Hz, 2H), 3.58 (s, 3H), 4.93 (s, 2H), 7.07 (t, J=7.6 Hz, 1H), 7.19 (t, J=7.1 Hz, 1H), 7.42-7.48 (m, 2H), 7.58 (d, J=7.9 Hz, 1H), 7.68 (dd, J=1.7, 8.7 Hz, 1H), 7.99 (s, 1H), 8.04 (d, J=9.0 Hz, 1H), 8.21 (d, J=8.7 Hz, 1H), 11.95-14.75 (bs, 1H); IR (neat) 3050, 2955, 2925, 2850, 1725, 1670, 1600, 1480, 1470, 1430, 1370, 1325, 1275, 1220, 1190, 1145, 1095, 1015, 980, 925, 895, 830, 800, 765, 735, 700, and 665 cm−1; mass spectrum [(+) ESI], m/z 480/482 (M+H)+;

후처리

  1. customhowever, two polar acids (one N—Me and one N—H) had been generated due to hydrolysis in these basic conditions
  2. concentrationAfter concentration
  3. waitAfter 1 h
  4. concentrationthe reaction mixture was concentrated
  5. additiondiluted with EtOAc (200 mL) and 1 N HCl (20 mL)
  6. washThe organic layer was washed with H2O (20 mL) and brine (20 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationAfter concentration
  9. customthe residue was purified by preparatory plate chromatography (10% MeOH:CHCl3)

출처 및 근거

ORD 기록
ord-c7cf7dde7643424a8b57726e09458e40
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07629377B2

반응 노트

불러오는 중…