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

HRID 1951528Notes

Reaction equation

HRID 1951528 reaction equation
[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[O:11][CH3:12])=O.[CH3:13][C:14]1[N:15]=[C:16]([CH2:19][C:20]([CH3:22])=[O:21])[S:17][CH:18]=1.N1CCCCC1.C(O)(=O)C>ClCCl>[CH3:12][O:11][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:3]=1[CH:1]=[C:19]([C:16]1[S:17][CH:18]=[C:14]([CH3:13])[N:15]=1)[C:20](=[O:21])[CH3:22])[C:7]#[N:8]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 166592514-Formyl-3-methoxybenzonitrileHCID 179309881-(4-Methyl-1,3-thiazol-2-yl)propan-2-one

Product 1

HCID 670179743-Methoxy-4-[2-(4-methyl-1,3-thiazol-2-yl)-3-oxobut-1-en-1-yl]benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

400 mg (2.48 mmol) of the compound from example 3A and 424 mg (2.73 mmol) of the compound from example 4A are dissolved in 10 ml of dichloromethane, and 0.245 ml (2.48 mmol) of piperidine and 0.142 ml (2.48 mmol) of acetic acid are added. The reaction mixture is heated under reflux with an inverse water trap overnight. The volatile components are then removed in a rotary evaporator, and the crude product is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). 390 mg (53% of theory) of the title compound are obtained as a mixture of the E/Z isomers.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureunder reflux with an inverse water trap overnight
  3. customThe volatile components are then removed in a rotary evaporator
  4. customthe crude product is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)

Sources & evidence

ORD record
ord-e81779485232458d80b39d8ea2fd17d8
Source dataset
uspto-grants-2013_03
Patent number
US08404723B2

Reaction notes

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