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

HRID 1951535Notes

Reaction equation

HRID 1951535 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][O:14][CH2:15][C:16]([CH2:18][C:19]1[S:20][CH:21]=[C:22]([CH3:24])[N:23]=1)=[O:17].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:18]([C:19]1[S:20][CH:21]=[C:22]([CH3:24])[N:23]=1)[C:16](=[O:17])[CH2:15][O:14][CH3:13])[C:7]#[N:8]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 166592514-Formyl-3-methoxybenzonitrileHCID 594923571-Methoxy-3-(4-methyl-1,3-thiazol-2-yl)acetone

Product 1

HCID 670179713-Methoxy-4-[4-methoxy-2-(4-methyl-1,3-thiazol-2-yl)-3-oxobut-1-en-1-yl]benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

500 mg (3.10 mmol) of the compound from example 3A and 632 mg (3.41 mmol) of the compound from example 13A are dissolved in 15 ml of dichloromethane, and 0.307 ml (3.10 mmol) of piperidine and 0.178 ml (3.10 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 preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). 200 mg (20% 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 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-3babeec99ec5427bbbe227fec341513a
Source dataset
uspto-grants-2013_03
Patent number
US08404723B2

Reaction notes

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