Sodium hydride → tert-Butyl 9,10-dichloro-6-[2-(4-fluorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1370435ノート

反応式

HRID 1370435 の反応式
[H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17][C:7]=3[C:6]=2[C:5]=1[Cl:25].[F:26][C:27]1[CH:36]=[CH:35][C:30]([O:31][CH2:32][CH2:33]Br)=[CH:29][CH:28]=1>CN(C=O)C>[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:33][CH2:32][O:31][C:30]3[CH:35]=[CH:36][C:27]([F:26])=[CH:28][CH:29]=3)[C:8]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:16][CH2:17][C:7]=3[C:6]=2[C:5]=1[Cl:25]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 20641711-(2-Bromoethoxy)-4-fluorobenzeneHCID 22396855tert-butyl 9,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

生成物 1

HCID 22396705tert-Butyl 9,10-dichloro-6-[2-(4-fluorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate収率 84.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Sodium hydride (60% dispersion in mineral oil, 68 mg, 1.7 mmol) was added to a solution of tert-butyl 9,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.40 g, 1.1 mmol) in DMF (6 mL). After 25 min, 4-fluorophenoxy ethyl bromide (0.34 mL, 2.3 mmol) was added. The reaction was quenched with saturated aqueous NH4Cl after 22 h and extracted with A EtOAc (3×15 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40M) with heptane/EtOAc (17:3) to give 0.46 g (82%) of a white solid: mp 163.5-165.5° C.; 1H NMR (300 MHz, CDCl3) δ 7.16 (m, 2H), 6.92 (m, 2H), 6.70 (m, 2H), 4.44 (m, 2H), 4.12 (m, 2H), 3.73 (m, 4H), 3.51 (m, 2H), 3.12 (m, 2H), 1.48 (s, 9H); IR (diffuse reflectance) 1675, 1507, 1449, 1405, 1365, 1354, 1298, 1249, 1242, 1221, 1209, 1170, 1120, 835, 828 cm−1; MS (FAB) m/z 493 (M+H+), 494, 493, 492, 439, 438, 437, 436, 435, 57, 42; HRMS (EI) calcd for C25H27Cl2FN2O3 492.1383, found 492.1385; Anal. Calcd for C25H27Cl2FN2O3: C, 60.86; H, 5.51; N, 5.68, found: C, 60.93; H, 5.60; N, 5.69.

後処理

  1. customThe reaction was quenched with saturated aqueous NH4Cl after 22 h
  2. extractionextracted with A EtOAc (3×15 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. customdecanted
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (Biotage, 40M) with heptane/EtOAc (17:3)

出典と根拠

ORDレコード
ord-fa3c7a4ddb624ca0894572f9a15a4bf2
出典データセット
uspto-grants-2003_06
特許番号
US06583135B2

反応ノート

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