Phenacyl bromide → Tert-butyl 4-methyl-3-(4-phenylthiazol-2-yl)piperazine-1-carboxylate

HRID 874969Notes

Reaction equation

HRID 874969 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[C:11]([CH:14]1[N:19]([CH3:20])[CH2:18][CH2:17][N:16]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15]1)(=[S:13])[NH2:12]>CCO>[CH3:20][N:19]1[CH2:18][CH2:17][N:16]([C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[CH2:15][CH:14]1[C:11]1[S:13][CH:2]=[C:3]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:12]=1

Participants

4

Reactant 2

HCID 6259Phenacyl bromideHCID 86673534HCID 86673534, compound

Product 1

HCID 70975633Tert-butyl 4-methyl-3-(4-phenylthiazol-2-yl)piperazine-1-carboxylateYield 64.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-bromoacetophenone (130 mg, 0.65 mmol) and tert-butyl 3-carbamothioyl-4-methylpiperazine-1-carboxylate (170 mg, 0.65 mmol) in EtOH (15 mL) was heated to 70° C. for 4 h. The reaction mixture was cooled to room temperature and solvent was evaporated under reduced pressure. The residue was diluted with water and the organic product was extracted with EtOAc. The combined extracts were washed with H2O and brine, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 20-25% EtOAc in petroleum ether) to afford tert-butyl 4-methyl-3-(4-phenylthiazol-2-yl)piperazine-1-carboxylate (150 mg, yield 64%). 1H NMR (300 MHz, CDCl3) δ 7.92-7.90 (m, 2H), 7.49 (m, 1H), 7.46-7.41 (m, 2H), 7.37-7.34 (m, 1H), 4.03-3.98 (m, 1H), 3.67-3.64 (m, 2H), 3.23-3.15 (m, 2H), 2.97-2.93 (m, 2H), 2.26 (s, 3H), 1.46 (s, 9H). MS (ESI) m/z: Calculated for C19H25N3O2S: 359.17. found: 360.2 (M+H)+

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customsolvent was evaporated under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionthe organic product was extracted with EtOAc
  5. washThe combined extracts were washed with H2O and brine
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 20-25% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-48d68d5e72474c058cf12631ab5ea7cc
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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