Methanol → α-[(Dimethylamino)methylene]-β-oxo-2-thiophenepropanenitrile

HRID 1018877Notes

Reaction equation

HRID 1018877 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:10][N:9]=[CH:8][CH:7]=1.CO[CH:13](OC)[N:14]([CH3:16])[CH3:15].CO>C1(C)C=CC=CC=1>[CH3:16][N:14]([CH:13]=[C:7]([C:6](=[O:10])[C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[C:8]#[N:9])[CH3:15]

Participants

5

Reactant 3

HCID 887MethanolHCID 78373Dimethylformamide dimethyl acetalHCID 120499865-(Thiophen-2-YL)-1,2-oxazole

Product 1

HCID 3743025α-[(Dimethylamino)methylene]-β-oxo-2-thiophenepropanenitrileYield 87.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 5-(2-thienyl)isoxazole (4.3 kg) and dimethylformamide dimethylacetal (6.1 kg; Lancaster) in toluene (12 L; Barton) is heated at reflux. As methanol forms it is removed by distillation. Solid forms from the reaction mixture. The reaction mixture is cooled and diluted with methyl-t-butyl ether (8 L; Van Waters). The precipitate is collected by filtration and washed with methyl-t-butyl ether (4 L). The solid is slurried with acetone (10 L; Batron) and hexanes (10 L; Mallinckrodt), then filtered and washed with hexanes (4 L). After drying in vacuo there is obtained 5.124 kg of α-[(dimethylamino)methylene]-β-oxo-2-thiophenepropane-nitrile (87% yield).

Workup

  1. temperatureis heated
  2. temperatureat reflux
  3. customis removed by distillation
  4. temperatureThe reaction mixture is cooled
  5. additiondiluted with methyl-t-butyl ether (8 L; Van Waters)
  6. filtrationThe precipitate is collected by filtration
  7. washwashed with methyl-t-butyl ether (4 L)
  8. filtrationfiltered
  9. washwashed with hexanes (4 L)
  10. customAfter drying in vacuo

Sources & evidence

ORD record
ord-a974815b42cd49c39cfba72813295f17
Source dataset
uspto-grants-2002_11
Patent number
US06485746B1

Reaction notes

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