Furan → 2-(4-(Furan-2-yl)-phenyl)-2-methyl-propionitrile

HRID 1359602Notes

Reaction equation

HRID 1359602 reaction equation
CN(CCN(C)C)C.[O:9]1[CH:13]=[CH:12][CH:11]=[CH:10]1.[Li]CCCC.Br[C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:30])([CH3:29])[C:27]#[N:28])=[CH:22][CH:21]=1>C1COCC1.CCOCC.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:30][C:26]([C:23]1[CH:24]=[CH:25][C:20]([C:10]2[O:9][CH:13]=[CH:12][CH:11]=2)=[CH:21][CH:22]=1)([CH3:29])[C:27]#[N:28]

Participants

9

Reactant 4

HCID 8029FuranHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 104435912-(4-Bromophenyl)-2-methylpropanenitrileHCID 178418339Butyllithium

Product 1

HCID 181825192-(4-(Furan-2-yl)-phenyl)-2-methyl-propionitrileYield 92.3%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

To a cooled (0° C.) mixture of TMEDA (11.4 mL, 76 mmol) and THF (75 mL) was added furan (5.7 mL, 78 mmol) followed by n-BuLi (15 mL, 2.5M in hexanes). The resulting solution was stirred for 30 min then ZnCl2 added (60 mL, 0.5M in THF). To this solution was added a solution comprised of (4-bromo-phenyl)-2,2-dimethyl-acetonitrile (4.48 g, 20 mmol) (reference example 30a) and (Ph3P)4Pd (460 mg, 0.4 mmol) in THF (10 mL). The resulting mixture was warmed to 50° C. and stirred at this temperature for 2.5 hr. The reaction mixture was allowed to cool to room temperature, diluted with ether, then washed, sequentially, with aqueous hydrochloric acid (2M) and brine, then dried over MgSO4 and concentrated. The residue was purified by flash chromatography (eluting with 10% ethyl acetate in hexanes) to give 3.9 g of the title compound as an oil. 1H NMR (CDCl3) d 1.74 (s, 6H), 6.47 (dd, J=2, 1 Hz, 1H), 6.66 (d, J=2 Hz, 1H), 7.47 (m, 3H), 7.68 (m, 2H), MS (EI) m/z 211 (M)+.

Workup

  1. temperatureTo a cooled
  2. additionTo this solution was added a solution
  3. stirringstirred at this temperature for 2.5 hr
  4. temperatureto cool to room temperature
  5. washwashed
  6. dry with materialsequentially, with aqueous hydrochloric acid (2M) and brine, then dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (eluting with 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-092d58000a9b4da59ac3ac485ffb92cc
Source dataset
uspto-grants-2003_07
Patent number
US06599918B2

Reaction notes

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