Cesium carbonate → HCID 59354806, compound

HRID 655424Notes

Reaction equation

HRID 655424 reaction equation
Br[C:2]1[C:3](=[O:16])[C:4]([CH3:15])([CH3:14])[O:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1.CC1(C)C(C)(C)OB([C:25]2[CH:42]=[CH:41][C:28]([O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)=[CH:27][CH:26]=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]>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:6]2[O:5][C:4]([CH3:15])([CH3:14])[C:3](=[O:16])[C:2]=2[C:25]2[CH:26]=[CH:27][C:28]([O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)=[CH:41][CH:42]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 59354807HCID 59354807, compound

Product 1

HCID 59354806HCID 59354806, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 4-bromo-5-(4-chlorophenyl)-2,2-dimethylfuran-3(2H)-one (1.0 g, 3.30 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (1.30 g, 3.60 mmol), and Cs2CO3 (5.37 g, 16.50 mmol) in toluene (10 mL) and water (5 mL) was degassed. Then, Pd(dppf)Cl2 (0.54 g, 0.601 mmol) was added under an inert atmosphere and the solution was degassed again. The reaction mixture 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-(4-chlorophenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (520 mg, 35%) as a pale yellow solid. 1H NMR (500 MHz, d6-DMSO): δ 8.44 (d, J=8.5 Hz, 1H), 8.02 (t, J=7.9 Hz, 2H), 7.81 (t, J=8.4 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.63 (t, J=8.2 Hz, 1H), 7.58 (d, J=8.5 Hz, 2H), 7.52 (d, J=8.5 Hz, 2H), 7.18 (d, J=7.4 Hz, 2H), 7.11 (d, J=7.5 Hz, 2H), 5.39 (s, 2H), 1.44 (s, 6H). MS: [M+Na]: m/z=478.1, [M+H]: m/z=456.1.HPLC: 97%, Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), AcN (B), Flow rate: 0.5 ml/min (Gradient).

Workup

  1. customthe solution was degassed again
  2. temperatureThe reaction mixture 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

Sources & evidence

ORD record
ord-7f796ec9f6fd4f2eaa7af3fece318710
Source dataset
uspto-grants-2011_12
Patent number
US08071595B2

Reaction notes

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