Acetyl chloride → (E)-4-[[3-[2-(4-cyclohexyl-2-thiazolyl)-ethenyl]phenyl]amino]-2,2-diethyl-4-oxobutanoic acid

HRID 359489Notes

Reaction equation

HRID 359489 reaction equation
[CH2:1]([C:3]([CH2:11][CH3:12])([CH2:7][C:8]([OH:10])=O)[C:4]([OH:6])=[O:5])[CH3:2].C(Cl)(=O)C.[CH:17]1([C:23]2[N:24]=[C:25](/[CH:28]=[CH:29]/[C:30]3[CH:31]=[C:32]([NH2:36])[CH:33]=[CH:34][CH:35]=3)[S:26][CH:27]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C([O-])(=O)C.[Na+]>COCCOC>[CH:17]1([C:23]2[N:24]=[C:25](/[CH:28]=[CH:29]/[C:30]3[CH:31]=[C:32]([NH:36][C:8](=[O:10])[CH2:7][C:3]([CH2:1][CH3:2])([CH2:11][CH3:12])[C:4]([OH:6])=[O:5])[CH:33]=[CH:34][CH:35]=3)[S:26][CH:27]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 1385662,2-Diethylbutanedioic acidHCID 517045Sodium AcetateHCID 15136084(E)-3-[2-[4-(cyclohexyl)-2-thiazolyl]-ethenyl]benzeneamine

Product 1

HCID 15136085(E)-4-[[3-[2-(4-cyclohexyl-2-thiazolyl)-ethenyl]phenyl]amino]-2,2-diethyl-4-oxobutanoic acidYield 30.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 9.26 g (53 mmol) of 2,2-diethylsuccinic acid and 30 ml of acetyl chloride was heated under reflux for 1.5 hr, cooled, and concentrated in vacuo. The residue was reconcentrated twice with toluene and then dissolved in 150 ml of 1,2-dimethoxyethane. To this solution was added 7.56 g (26.4 mmol) of the (E)-3-[2-[4-(cyclohexyl)-2-thiazolyl]-ethenyl]benzeneamine and 10.9 g of sodium acetate dissolved in 150 ml of 1,2-dimethoxyethane. This reaction mixture was heated on the steam bath for 3.5 hr and then concentrated in vacuo. The residue was digested with 600 ml of water on the steam bath for 20 min. The solid was collected to give 10 g of crude product. Recrystallization from ethanol gave 3.5 g of product, mp 180°-185°. Further recrystallization from methanol gave (E)-4-[[3-[2-(4-cyclohexyl-2-thiazolyl)-ethenyl]phenyl]amino]-2-methylene-4-oxobutanoic acid as off-white needles, mp 187°-189°.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1.5 hr
  3. temperaturecooled
  4. concentrationconcentrated in vacuo
  5. dissolutiondissolved in 150 ml of 1,2-dimethoxyethane
  6. temperatureThis reaction mixture was heated on the steam bath for 3.5 hr
  7. concentrationconcentrated in vacuo
  8. customThe solid was collected
  9. customto give 10 g of crude product
  10. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-373d13b92c0b4bdaa7f2e0d08449dc2a
Source dataset
uspto-grants-1991_03
Patent number
US05001140

Reaction notes

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