Diisopropylethylamine → 2-Ethoxycarbonyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene)piperidin-1-yl]ethyl]thiazole hydrochloride

HRID 1276477Notes

Reaction equation

HRID 1276477 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([CH2:18][CH2:19][Cl:20])=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:10]=1)=[O:5])[CH3:2].Cl.[F:22][C:23]1[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=1)[CH:26]=[C:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(CC)C(C)C)(C)C>C(O)C>[ClH:20].[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([CH2:18][CH2:19][N:30]2[CH2:31][CH2:32][C:27](=[CH:26][C:25]3[CH:33]=[CH:34][CH:35]=[C:23]([F:22])[CH:24]=3)[CH2:28][CH2:29]2)=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 154810512-Ethoxycarbonyl-4-(4-fluorophenyl)-5-(2-chloroethyl)thiazoleHCID 217017174-((3-Fluorophenyl)methylidene)piperidine hydrochloride

Product 1

HCID 221158682-Ethoxycarbonyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene)piperidin-1-yl]ethyl]thiazole hydrochlorideYield 47.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1.50 g of 2-ethoxycarbonyl-4-(4-fluorophenyl)-5-(2-chloroethyl)thiazole, 1.10 g of 4-(3-fluorobenzylidene)piperidine hydrochloride and 2.50 g of N,N-diisopropylethylamine were stirred in 3 ml of ethanol at 80° C. for 40 hours. The reaction solution was concentrated under reduced pressure, and the residue was treated with ethyl acetate and saturated aqueous sodium bicarbonate to effect separation of layers. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and then the drying agent was removed by filtration. The resulting filtrate was concentrated under reduced pressure, and the residue was purified by a flash column chromatography (Wako Gel C200 (manufactured by Wako Pure Chemical Industries), eluant: hexane-ethyl acetate-5.1) and then Chromatolex NH NHDM1020 (manufactured by Fuji Division Chemical), eluant: hexane-ethyl acetate=10.1). This product was treated with 4 N hydrogen chloride/1.4-dioxane solution and then recrystallized from ethanol to obtain 1.14 g of 2-ethoxycarbonyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene)piperidin-1-yl]ethyl]thiazole hydrochloride

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionthe residue was treated with ethyl acetate and saturated aqueous sodium bicarbonate
  3. customseparation of layers
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe drying agent was removed by filtration
  7. concentrationThe resulting filtrate was concentrated under reduced pressure
  8. customthe residue was purified by a flash column chromatography (Wako Gel C200 (manufactured by Wako Pure Chemical Industries), eluant: hexane-ethyl acetate-5.1)
  9. additionThis product was treated with 4 N hydrogen chloride/1.4-dioxane solution
  10. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-04190490e8ae4a4891f849a4d4a7d717
Source dataset
uspto-grants-2000_12
Patent number
US06166033

Reaction notes

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