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

HRID 1882139노트

반응식

HRID 1882139 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
110 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-a9ff8a4d49a94ccdb89c33a614935186
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08318928B2

반응 노트

불러오는 중…