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

HRID 1798678Notes

Reaction equation

HRID 1798678 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.[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=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]>[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[C:3](=[O:15])[C:4]([CH3:14])([CH3:13])[O:5][C:6]=2[C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 50574272-[4-(Benzyloxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 593548244-bromo-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one

Product 1

HCID 595801534-(4-(benzyloxy)phenyl)-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-oneYield 60.2%

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-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one (10.0 g, 37.2 mmol), 2-(4-(benzyloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (13.8 g, 44.7 mmol), and Cs2CO3 (36.27 g, 111.6 mmol) in toluene (100 mL) and water (50 mL) was degassed. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (2.7 g, 3.7 mmol) was added under an inert atmosphere and again degassed. Then the reaction was refluxed for 3 h and monitored by TLC. Upon complete consumption of the starting material, the reaction mixture was filtered through a bed of Celite® washing with ethyl acetate. The organic layer was then washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 20% ethyl acetate in n-hexanes on 230-400 mesh silica gel to afford 4-(4-(benzyloxy)phenyl)-2,2-dimethyl-5-(pyridin-4-yl)furan-3(2H)-one (8.3 g, 60.2%) as a light orange color solid. 1H NMR, 500 MHz, DMSO-d6: δ 8.2 (d, 2H), 7.85 (d, 2H), 7.6 (d, 4H), 7.4 (t, 1H), 7.15 (d, 2H), 7.05 (d, 2H), 5.1 (s, 2H), 1.45 (s, 6H). MS: [M+H]+: m/z=396.0. HPLC: (97.5%, 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).

Workup

  1. customagain degassed
  2. temperatureThen the reaction was refluxed for 3 h
  3. customUpon complete consumption of the starting material
  4. filtrationthe reaction mixture was filtered through a bed of Celite®
  5. washwashing with ethyl acetate
  6. washThe organic layer was then washed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-8a93c6137d974f8c8c842b5eb8a17e97
Source dataset
uspto-grants-2013_01
Patent number
US08343973B2

Reaction notes

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