4-[(2-Methylbut-3-yn-2-yl)oxy]benzonitrile → HCID 19895647, compound

HRID 892600Notes

Reaction equation

HRID 892600 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[CH2:9][CH:8]([C:14]3[CH:15]=[N+:16]([O-])[CH:17]=[CH:18][CH:19]=3)[C:7]=2[CH:21]=1)#[N:2].CC1(C)CC(C2C=CC=CN=2)C2C=C(C(O)=O)C=CC=2O1.CC(C)(OC1C=CC(C#N)=CC=1)C#C>C(NCC)C.[Pd](Cl)Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:12][C:10]([CH3:13])([O:11][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:21][CH:7]=1)[C:9]#[C:8][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 3

HCID 27790724-[(2-Methylbut-3-yn-2-yl)oxy]benzonitrileHCID 150389033,4-dihydro-2,2-dimethyl-4-(2-pyridyl)-2H-1-benzopyran-6-carboxylic acidHCID 54331976HCID 54331976, compound

Product 1

HCID 19895647HCID 19895647, compound

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8021DiethylamineSolvent

Procedure

The 3-(6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)pyridine N-oxide used as the starting material was prepared as follows: (A) 10.25 g of 3-iodopyridine were added at room temperature to a solution of 44 mg of palladium(II) chloride, 131 mg of triphenylphosphine and 95 mg of copper(I) iodide in 200 mg of diethylamine. 9.25 g of 4-(1,1-dimethyl-2-propynyloxy)benzonitrile were then added and the mixture was stirred for 3 days. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was dried over sodium sulphate and evaporated. The residue was chromatographed on silica gel using ethyl acetate/petroleum ether (11:9) for the elution to give 11.8 g of 4-[1,1-dimethyl-3-(3-pyridyl)-2-propynyloxy]benzonitrile in the form of an oil. (B) 11.8 g of 4-[1,1-dimethyl-3-(3-pyridyl)-2-propynyloxy]benzonitrile were heated at reflux in 75 ml of 1,2-dichlorobenzene for 3.5 hours. The reaction mixture was allowed to cool to room temperature and was then evaporated. The residue was chromatographed on silica gel using ethyl acetate for the elution. After recrystallization from cyclohexane there were obtained 6.7 g of 2,2-dimethyl-4-(3-pyridyl)-2H-1-benzopyran-6-carbonitrile of melting point 98°-99° C. (C) 2.1 g of 2,2-dimethyl-4-(3-pyridyl)-2H-1-benzopyran-6-carbonitrile were dissolved in 50 ml of ethyl acetate and shaken at room temperature under a hydrogen atmosphere with 50 mg of 10% palladium-on-charcoal for a total of 30 hours with several changes of catalyst. The mixture was filtered and the filtrate was evaporated. The residue was chromatographed on silica gel using ethyl acetate for the elution. 910 mg of 3,4-dihydro-2,2-dimethyl-4-(3-pyridyl)-2H-1-benzopyran-6-carbonitrile were obtained in the form of an oil. (D) 610 mg of m-chloroperbenzoic acid were added to a solution of 792 mg of 3,4-dihydro-2,2-dimethyl-4-(3-pyridyl)-2H-1-benzopyran-6-carbonitrile in 15 ml of dichloromethane. After stirring at room temperature for one hour the mixture was washed with sodium bisulphite solution and sodium bicarbonate solution. The organic phase was dried over sodium sulphate and evaporated. The residue was crystallized from t-butyl methyl ether to give 710 mg of 3-(6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)pyridine N-oxide in the form of a solid of melting point 134°-137° C.

Workup

  1. customwas prepared
  2. customThe mixture was evaporated
  3. customthe residue was partitioned between ethyl acetate and water
  4. dry with materialThe organic phase was dried over sodium sulphate
  5. customevaporated
  6. customThe residue was chromatographed on silica gel
  7. washfor the elution

Sources & evidence

ORD record
ord-1880dd181b684256a525aa4a6a7d0bc1
Source dataset
uspto-grants-1992_06
Patent number
US05118694

Reaction notes

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