Water → Ethyl 1-(4-bromo-2-iodobenzyl)-4-(trifluoromethyl)cyclohexanecarboxylate

HRID 539307ノート

反応式

HRID 539307 の反応式
[F:1][C:2]([F:15])([F:14])[CH:3]1[CH2:8][CH2:7][CH:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4]1.C([N-]C(C)C)(C)C.[Li+].[Br:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31]Br)=[C:27]([I:33])[CH:26]=1.O>C1COCC1.CCOC(C)=O>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][C:6]2([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4][CH:3]([C:2]([F:14])([F:15])[F:1])[CH2:8][CH2:7]2)=[C:27]([I:33])[CH:26]=1

参加物

7

反応物 4

HCID 962WaterHCID 2724682Lithium diisopropylamideHCID 22182861Ethyl 4-(trifluoromethyl)cyclohexane-1-carboxylate2 回HCID 532313074-Bromo-1-(bromomethyl)-2-iodobenzene

生成物 1

HCID 67979570Ethyl 1-(4-bromo-2-iodobenzyl)-4-(trifluoromethyl)cyclohexanecarboxylate収率 69%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

Ethyl 4-(trifluoromethyl)cyclohexanecarboxylate (Intermediate 76, 1.492 g, 6.65 mmol) was dissolved in THF (25 mL). The atmosphere was exchanged to argon, and the solution was cooled to −78° C. Lithium diisopropylamide (1.8 M in THF/heptane/ethylbenzene) (4.07 mL, 7.32 mmol) was added, while the temperature was kept at −78° C. The solution was stirred for 30 min at −78° C. 4-Bromo-1-(bromomethyl)-2-iodobenzene (see Caruso, A.; Tovar, J., D. J. Org. Chem. 2011, 76, 2227-2239, 2.50 g, 6.65 mmol) in THF (25 mL) was added via a syringe. The mixture was allowed to reach r.t., while stirred for 2 h. Water (10 mL) was added to the reaction mixture, followed by EtOAc (40 mL). The phases were separated. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (eluent: heptane/EtOAc 95/5) to give the title compound (2.41 g, 69% yield): 1H NMR (400 MHz, CDCl3) δ ppm 1.22-1.27 (m, 3 H) 1.29-1.43 (m, 4 H) 1.82-1.90 (m, 2 H) 1.82-1.90 (m, 3 H) 1.97 (br. s., 2 H) 2.28-2.36 (m, 3 H) 3.01 (s, 3 H) 4.18 (q, 3 H) 6.91 (m, 1 H) 7.38 (m, 1 H) 7.99 (m, 1 H); MS (ES+) m/z 520 [M+H]+.

後処理

  1. customwas kept at −78° C
  2. customto reach r.t.
  3. stirringwhile stirred for 2 h
  4. customThe phases were separated
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (eluent: heptane/EtOAc 95/5)

出典と根拠

ORDレコード
ord-1c671463311b48c7ab3b04b46aa56138
出典データセット
uspto-grants-2014_10
特許番号
US08865911B2

反応ノート

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