Cesium carbonate → 2,2-dimethyl-5-(pyridin-4-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one

HRID 1258287Notes

Reaction equation

HRID 1258287 reaction equation
Br[C:2]1[C:3](=[O:15])[C:4]([CH3:14])([CH3:13])[O:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1.CC1(C)C(C)(C)OB([C:24]2[CH:41]=[CH:40][C:27]([O:28][CH2:29][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=3)=[CH:26][CH:25]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>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].C1(C)C=CC=CC=1.O>[CH3:13][C:4]1([CH3:14])[C:3](=[O:15])[C:2]([C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=3)=[CH:40][CH:41]=2)=[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[O:5]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593548244-bromo-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one

Product 1

HCID 445940362,2-dimethyl-5-(pyridin-4-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-oneYield 74%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 22272177Toluene waterSolvent

Procedure

A solution of 4-bromo-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one (0.25 g, 0.93 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.37 g, 1.026 mmol), and Cs2CO3 (1.52 g, 4.664 mmol) in 5:1 toluene/water (12 mL) was degassed. Then, Pd(dppf)Cl2 (152.2 mg, 0.18 mmol) was added under an inert atmosphere and the solution was degassed again. The reaction mixture was then refluxed for 3 h, filtered through a pad of Celite® and the filtrate was diluted with EtOAc (100 mL). The combined organics were washed with water (50 mL) and brine (50 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 2,2-dimethyl-5-(pyridin-4-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (0.29 g, 74%) as a solid. 1H NMR (500 MHz, CDCl3): δ 8.78 (d, J=7.2 Hz, 1 H), 8.56-8.50 (m, 2 H), 8.15-8.05 (m, 2 H), 7.78-7.72 (m, 1 H), 7.63-7.59 (m, 1 H), 7.56-7.47 (m, 2 H); 7.18-7.09 (m, 2 H), 7.02-6.96 (m, 3 H), 5.40 (s, 2 H), 1.50 (s, 6 H). MS: M+H: m/z=423.1. LC-MS: 98%, Column: Eclipse XDB—C18, 150×4.6 mm, 5 um. Mobile Phase: 0.1% TFA in Water (A), AcN (B), Flow rate: 1.5 ml/min (Gradient).

Workup

  1. customthe solution was degassed again
  2. temperatureThe reaction mixture was then refluxed for 3 h
  3. filtrationfiltered through a pad of Celite®
  4. additionthe filtrate was diluted with EtOAc (100 mL)
  5. washThe combined organics were washed with water (50 mL) and brine (50 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

Sources & evidence

ORD record
ord-29e1b961b92e42c0a4c2b98c51392702
Source dataset
uspto-grants-2013_06
Patent number
US08466148B2

Reaction notes

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