Cesium carbonate → HCID 59354858, compound

HRID 1776372Notes

Reaction equation

HRID 1776372 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.[CH3:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:26]=2)=[N:21][CH:22]=1.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]>[CH3:13][C:4]1([CH3:14])[C:3](=[O:15])[C:2]([C:28]2[CH:27]=[CH:26][C:25]([O:24][CH2:23][C:20]3[CH:19]=[CH:18][C:17]([CH3:16])=[CH:22][N:21]=3)=[CH:30][CH:29]=2)=[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[O:5]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 593548244-bromo-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-oneHCID 59354843HCID 59354843, compound

Product 1

HCID 59354858HCID 59354858, compoundYield 53.3%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 4-bromo-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one (0.11 g, 0.34 mmol), 5-methyl-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)pyridine (0.1 g, 0.37 mmol), and Cs2CO3 (0.55 g, 1.86 mmol) in toluene (7 mL) and water (3 mL) was degassed, Pd(dppf)Cl2 (0.058 g, 0.07 mmol) was added under an inert atmosphere and the mixture was degassed again. Then the reaction was refluxed for 2 h and was filtered through a pad of Celite®. The filtrate was diluted with EtOAc (50 mL), washed with water (20 mL), 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 2,2-dimethyl-4-(4-((5-methylpyridin-2-yl)methoxy)phenyl)-5-(pyridin-4-yl)furan-3(2H)-one (70 mg, 48%) as a solid, 1H NMR (500 MHz, d6-DMSO): δ 8.72 (d, J=8.5 Hz, 2 H), 8.42 (t, J=7.9 Hz, 1 H), 7.70 (d, J=8.2 Hz, 2 H), 7.63 (t, J=8.2 Hz, 1 H), 7.52-7.43 (m, 3 H), 7.18 (d, J=7.4 Hz, 2 H), 7.11 (d, J=7.5 Hz, 2 H), 5.18 (s, 2 H), 2.35 (s,3H) , 1.54 (s, 6 H). MS: [M+H]: m/z=387.0. HPLC: 91.4% (RT-1.73 min), 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. customwas degassed
  2. customthe mixture was degassed again
  3. temperatureThen the reaction was refluxed for 2 h
  4. filtrationwas filtered through a pad of Celite®
  5. additionThe filtrate was diluted with EtOAc (50 mL)
  6. washwashed with water (20 mL), brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto obtain the crude product
  11. customThe crude material was purified via silica gel column chromatography

Sources & evidence

ORD record
ord-82d86436e3b145b5badcd551c83c0195
Source dataset
uspto-grants-2016_02
Patent number
US09265767B2

Reaction notes

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