Acetic Acid → 4-[2-(4-Ethyl-1,3-thiazol-2-yl)-3-oxobut-1-en-1-yl]-3-methoxybenzonitrile

HRID 1951554Notes

Reaction equation

HRID 1951554 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.[CH2:13]([C:15]1[N:16]=[C:17]([CH2:20][C:21]([CH3:23])=[O:22])[S:18][CH:19]=1)[CH3:14].N1CCCCC1.C(O)(=O)C>ClCCl>[CH2:13]([C:15]1[N:16]=[C:17]([C:20]([C:21](=[O:22])[CH3:23])=[CH:1][C:3]2[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=2[O:11][CH3:12])[S:18][CH:19]=1)[CH3:14]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 166592514-Formyl-3-methoxybenzonitrileHCID 594923381-(4-Ethyl-1,3-thiazol-2-yl)acetone

Product 1

HCID 670179904-[2-(4-Ethyl-1,3-thiazol-2-yl)-3-oxobut-1-en-1-yl]-3-methoxybenzonitrileYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

770 mg (4.78 mmol) of the compound from example 3A and 890 mg (5.26 mmol) of the compound from example 17A are dissolved in 15 ml of dichloromethane, and 0.473 ml (4.78 mmol) of piperidine and 0.247 ml (4.78 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 MPLC (Biotage 12M cartridge, eluent: isohexane/ethyl acetate 80:20→70:30). 920 mg (66% of theory) of 4-[2-(4-ethyl-1,3-thiazol-2-yl)-3-oxobut-1-en-1-yl]-3-methoxybenzonitrile are obtained as a mixture of the E/Z isomers {LC-MS (Method 1): Rt=2.39 min; (Elpos): m/z=313 [M+H]+} and without further working up.

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 MPLC (Biotage 12M cartridge, eluent: isohexane/ethyl acetate 80:20→70:30)

Sources & evidence

ORD record
ord-0a372f61b8ff467184e8bc10b907afc7
Source dataset
uspto-grants-2013_03
Patent number
US08404723B2

Reaction notes

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