Cesium carbonate → 4-(3-(4-(Benzyloxy)phenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrile

HRID 1798685Notes

Reaction equation

HRID 1798685 reaction equation
Br[C:2]1[C:6](=[O:7])[C:5]([CH3:9])([CH3:8])[O:4][C:3]=1[C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=1.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=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]>[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[C:6](=[O:7])[C:5]([CH3:9])([CH3:8])[O:4][C:3]=2[C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[CH:28][CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 50574272-[4-(Benzyloxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 66643774HCID 66643774, compound

Product 1

HCID 666439234-(3-(4-(Benzyloxy)phenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrileYield 74.25%

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-(3-bromo-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrile (29.0 g, 107.4 mmol), 2-(4-(benzyloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (34.7 g, 118.8 mmol), and Cs2CO3 (104.7 g, 322.2 mmol) in toluene (200 mL) and water (50 mL) was degassed. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (8.5 g, 10 mmol) was added under an inert atmosphere and the solution was again degassed. The reaction was then refluxed for 3 h and monitored for completion 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-hexane on 230-400 mesh silica gel (Rf=0.3) to afford 4-(3-(4-(benzyloxy)phenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzonitrile (31.5 g, 74.25%) as solid. 1H NMR: 500 MHz, DMSO-d6: δ 7.95 (d, 2H), 7.75 (d, 2H), 7.5 (d, 4H), 7.35 (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: (99.5%, 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. customthe solution was again degassed
  2. temperatureThe reaction was then 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-ebd253a0fd384c4da1ad56e30d378347
Source dataset
uspto-grants-2013_01
Patent number
US08343973B2

Reaction notes

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