Acetic Acid → 3-Methoxy-4-[2-(5-methyl-1,3,4-thiadiazol-2-yl)-3-oxobut-1-en-1-yl]benzonitrile

HRID 1951543Notes

Reaction equation

HRID 1951543 reaction equation
[CH3:1][C:2]1[S:6][C:5]([CH2:7][C:8]([CH3:10])=[O:9])=[N:4][N:3]=1.[CH:11]([C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=1[O:21][CH3:22])=O.N1CCCCC1.C(O)(=O)C>ClCCl>[CH3:22][O:21][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:13]=1[CH:11]=[C:7]([C:5]1[S:6][C:2]([CH3:1])=[N:3][N:4]=1)[C:8](=[O:9])[CH3:10])[C:17]#[N:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 131041141-(5-Methyl-1,3,4-thiadiazol-2-yl)propan-2-oneHCID 166592514-Formyl-3-methoxybenzonitrile

Product 1

HCID 670179873-Methoxy-4-[2-(5-methyl-1,3,4-thiadiazol-2-yl)-3-oxobut-1-en-1-yl]benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1.34 g (8.32 mmol) of 1-(5-methyl-1,3,4-thiadiazol-2-yl)acetone [T. Saito et al., J. Heterocycl. Chem. 20, 73-75 (1983)] and 1.30 g (8.32 mmol) of the compound from example 3A are dissolved in 20 ml of dichloromethane, and 0.165 ml (1.66 mmol) of piperidine and 0.100 ml (1.66 mmol) of acetic acid are added. The reaction mixture is heated under reflux with an inverse water trap overnight. The volatile components are removed in a rotary evaporator, and the crude product is purified by column chromatography (silica gel; eluent: initially dichloromethane, then cyclohexane/ethyl acetate 4:1→1:1). 1.17 g (47% of theory) of the title compound are obtained as a mixture of the E/Z isomers which can be crystallized from ethyl acetate/n-pentane. 530 mg of the title compound are obtained as a crystalline solid in this way.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureunder reflux with an inverse water trap overnight
  3. customThe volatile components are removed in a rotary evaporator
  4. customthe crude product is purified by column chromatography (silica gel

Sources & evidence

ORD record
ord-67c269a490874675afa8e8a1c726ad43
Source dataset
uspto-grants-2013_03
Patent number
US08404723B2

Reaction notes

Loading…