Cesium carbonate → 5-(5,5-Dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile

HRID 655455노트

반응식

HRID 655455 반응식
Br[C:2]1[C:6](=[O:7])[C:5]([CH3:9])([CH3:8])[O:4][C:3]=1[C:10]1[CH:11]=[CH:12][C:13]([O:18][CH3:19])=[C:14]([CH:17]=1)[C:15]#[N:16].CC1(C)C(C)(C)OB([C:28]2[CH:45]=[CH:44][C:31]([O:32][CH2:33][C:34]3[CH:43]=[CH:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:35]=3)=[CH:30][CH:29]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:8][C:5]1([CH3:9])[O:4][C:3]([C:10]2[CH:11]=[CH:12][C:13]([O:18][CH3:19])=[C:14]([CH:17]=2)[C:15]#[N:16])=[C:2]([C:28]2[CH:29]=[CH:30][C:31]([O:32][CH2:33][C:34]3[CH:43]=[CH:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:35]=3)=[CH:44][CH:45]=2)[C:6]1=[O:7]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593548145-(3-Bromo-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile

생성물 1

HCID 445944675-(5,5-Dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile수율 58%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

A solution of 5-(3-bromo-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)-2-methoxybenzonitrile (0.15 g, 0.465 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.17 g, 0.465 mmol), and Cs2CO3 (0.75 g, 2.32 mmol) in toluene (6 mL) and water (3 mL) was degassed. Then, Pd(dppf)Cl2 (0.76 g, 0.090 mmol) was added under an inert atmosphere and the solution was again degassed. The reaction was then refluxed for 2 h, filtered through a pad of Celite® and the filtrate was diluted with EtOAc (40 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 5-(5,5-dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4, 5-dihydrofuran-2-yl)-2-methoxybenzonitrile (125 mg, 58%) as a pale yellow solid. 1H NMR (500 MHz, d6-DMSO): δ 8.43 (d, J=8.5 Hz, 1H), 8.02 (t, J=7.9 Hz, 2H), 7.90 (s, 1H), 7.81-7.77 (m, 2H), 7.70 (d, J=8.2 Hz, 1H), 7.62 (t, J=8.2 Hz, 1H), 7.32 (d, J=8.1 Hz, 1H), 7.19 (d, J=7.4 Hz, 2H), 7.12 (d, J=7.5 Hz, 2H), 5.40 (s, 2H), 3.95 (s, 3H), 1.46 (s, 6H). MS: [M+Na]: m/z=499.3, [M+H]: m/z=477.2. HPLC: 98%,

후처리

  1. customthe solution was again degassed
  2. temperatureThe reaction was then refluxed for 2 h
  3. filtrationfiltered through a pad of Celite®
  4. additionthe filtrate was diluted with EtOAc (40 mL)
  5. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto obtain the crude product
  10. customThe crude material was purified via silica gel column chromatography

출처 및 근거

ORD 기록
ord-c2dc326f6b9b43989100e4e45cbebbb6
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071595B2

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