Isovanillin → 3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-4-methoxybenzonitrile

HRID 549065Notes

Reaction equation

HRID 549065 reaction equation
O=[CH:2][C:3]1[CH:11]=[CH:10][C:7]([O:8][CH3:9])=[C:5]([OH:6])[CH:4]=1.Cl.[NH2:13]O.[H-].[Na+].[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C)C=O.O1CCCC1>[Si:17]([O:6][C:5]1[CH:4]=[C:3]([CH:11]=[CH:10][C:7]=1[O:8][CH3:9])[C:2]#[N:13])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]

Participants

7

Reactant 4

HCID 12127IsovanillinHCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 443297Hydroxyamine hydrochloride

Product 1

HCID 224774033-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-4-methoxybenzonitrileYield 84.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of iso-vanillin (10.0 g) in dimethylformamide (100 mL) was treated with hydroxylamine hydrochloride (9.14 g) and heated under reflux for 1 hour. The dimethylformamide was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The aqueous fraction was exhaustively extracted with ethyl acetate and the combined organic fractions were dried over sodium sulfate and concentrated in vacuo to afford a brown solid, which was dissolved in tetrahydrofuran (200 mL). After treatment with sodium hydride (2.8 g), the reaction mixture was stirred at room temperature for 1 hour. A solution of tert-butyldimethylsilyl chloride (10.9 g) in tetrahydrofuran (50 mL) was added and the mixture stirred under nitrogen overnight. The mixture was partitioned between water and diethyl ether. The organic extract was dried over sodium sulfate, concentrated in vacuo and subjected to flash column chromatography on silica eluting with a mixture of pentane and dichloromethane (1:3, v/v) to give the title compound (14.7 g) as a colourless oil which was used immediately in the next reaction. 1H NMR [(CD3)2SO]: δ 7.30 (1H, d, J=8.0 Hz); 7.11 (1H, s); 7.01 (1H, s); 3.70 (3H, s); 0.81 (9H, s); 0.01 (6H, s).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 1 hour
  3. customThe dimethylformamide was removed under reduced pressure
  4. customthe residue partitioned between ethyl acetate and water
  5. extractionThe aqueous fraction was exhaustively extracted with ethyl acetate
  6. dry with materialthe combined organic fractions were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto afford a brown solid, which
  9. customThe mixture was partitioned between water and diethyl ether
  10. extractionThe organic extract
  11. dry with materialwas dried over sodium sulfate
  12. concentrationconcentrated in vacuo
  13. additionsubjected to flash column chromatography on silica eluting with a mixture of pentane and dichloromethane (1:3

Sources & evidence

ORD record
ord-30db1dc4218a407a9951a15ada4b7591
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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