Ethanol → Ethyl 3-(4-(4-fluorophenyl)thiazol-2-yl)propanoate

HRID 1397301Notes

Reaction equation

HRID 1397301 reaction equation
[NH2:1][C:2](=[S:9])[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].[CH:10]1[C:15]([C:16]([CH2:18]Br)=O)=[CH:14][CH:13]=[C:12]([F:20])[CH:11]=1.[CH3:21]CO>>[F:20][C:12]1[CH:13]=[CH:14][C:15]([C:16]2[N:1]=[C:2]([CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:21])=[O:6])[S:9][CH:18]=2)=[CH:10][CH:11]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 967492-Bromo-1-(4-fluorophenyl)ethan-1-oneHCID 18333020Methyl 4-amino-4-thioxobutanoate

Product 1

HCID 67324988Ethyl 3-(4-(4-fluorophenyl)thiazol-2-yl)propanoateYield 7%

Procedure

A mixture of methyl 4-amino-4-thioxobutanoate (0.3 g, 2.03 mmol) and 2-bromo-4-fluoroacetophenone (0.440 g, 2.03 mmol) in EtOH (10 mL) was refluxed for 3 h. The reaction mixture was cooled to room temperature and solvent was removed under reduced pressure. The organic product was extracted with EtOAc and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 8-10% EtOAc in petroleum ether) to afford ethyl 3-(4-(4-fluorophenyl)thiazol-2-yl)propanoate (0.45 g, crude containing 7% of methyl ester product), which was carried through without further purification. 1H NMR (300 MHz, CDCl3) δ 7.88-7.83 (m, 2H), 7.28 (s, 1H), 7.13-7.07 (t, J=8.8 Hz, 2H), 4.22-4.15 (q, J=7.0 Hz, 2H), 3.40-3.35 (t, J=7.3 Hz, 2H), 2.93-2.88 (t, J=7.3 Hz, 2H), 1.30-1.25 (t, J=7.1 Hz, 3H). MS (ESI) m/z: Calculated for C14H14FNO2S: 279.07. found: 280.2 (M+H)+.

Workup

  1. temperaturewas refluxed for 3 h
  2. customsolvent was removed under reduced pressure
  3. extractionThe organic product was extracted with EtOAc
  4. washthe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 8-10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-f04b368cbc484251855c2626ac1c8374
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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