Cesium carbonate → Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-(2,2-dimethylpropoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

HRID 1882139ノート

反応式

HRID 1882139 の反応式
[F:1][CH:2]([F:26])[O:3][C:4]1[C:5]([OH:25])=[C:6](/[CH:10]=[CH:11]/[C:12]2[N:13]=[C:14]3[N:18]([C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[CH:16][S:15]3)[CH:7]=[CH:8][CH:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36]>CN(C)C=O.C(OCC)(=O)C.O>[F:26][CH:2]([F:1])[O:3][C:4]1[C:5]([O:25][CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[C:6](/[CH:10]=[CH:11]/[C:12]2[N:13]=[C:14]3[N:18]([C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[CH:16][S:15]3)[CH:7]=[CH:8][CH:9]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 124151-Bromo-2,2-dimethylpropaneHCID 59369921Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-hydroxyphenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

生成物 1

HCID 68406305Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-(2,2-dimethylpropoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate収率 63.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

To a stirred solution of Intermediate 6 (1.60 g, 4.209 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added cesium carbonate (2.74 g, 8.418 mmol) followed by 1-bromo-2,2-dimethylpropane (1.60 mL, 12.629 mmol) at room temperature. The resulting suspension was stirred at 110° C. overnight under nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (200 mL) and water (100 mL). The layers were separated. Aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined organic layers were washed with brine (2×50 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure. The residue obtained after the evaporation of the solvent was purified by silica gel column chromatography using 10% ethyl acetate in petroleum ether to obtain 1.20 g of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.07 (s, 9H), 1.39 (t, J=6.9 Hz, 3H), 3.57 (s, 2H), 4.35-4.42 (m, 2H), 7.18 (t, J=74.7 Hz, 1H), 7.20-7.25 (m, 2H), 7.47 (d, J=3.9 Hz, 1H), 7.52-7.58 (m, 1H), 7.73 (d, J=16.2 Hz, 1H), 7.90 (d, J=16.2 Hz, 1H), 8.10-8.16 (m, 1H); APCI-MS (m/z) 451.10 (MH)+.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionAqueous layer was extracted with ethyl acetate (2×50 mL)
  4. washthe combined organic layers were washed with brine (2×50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe residue obtained
  9. customafter the evaporation of the solvent
  10. customwas purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-a9ff8a4d49a94ccdb89c33a614935186
出典データセット
uspto-grants-2012_11
特許番号
US08318928B2

反応ノート

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