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

HRID 392301ノート

反応式

HRID 392301 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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), 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)+;

後処理

  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)

出典と根拠

ORDレコード
ord-dd62aa6c15ec47448840232b89cd457f
出典データセット
uspto-grants-2004_10
特許番号
US06800654B2

反応ノート

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