p-Toluenesulfonic acid → (2z)-2-(3-Butyl-1,3-thiazol-2(3h)-ylidene)-1-(5-chloro-2-methoxyphenyl)ethanone

HRID 448086

Reaction equation

HRID 448086 reaction equation
[H-].[Na+].[CH3:3][C:4]([C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[O:13][CH3:14])=[O:5].[CH2:15]([N:19]=[C:20]=[S:21])[CH2:16][CH2:17][CH3:18].Br[CH2:23][CH:24](OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.[Cl-].[Na+].O>[CH2:15]([N:19]1[CH:24]=[CH:23][S:21]/[C:20]/1=[CH:3]\[C:4]([C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[O:13][CH3:14])=[O:5])[CH2:16][CH2:17][CH3:18]

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 11613Butyl IsothiocyanateHCID 24758Sodium hydrideHCID 816722-Bromo-1,1-dimethoxyethaneHCID 2404341-(5-Chloro-2-methoxyphenyl)ethanone

Product 1

HCID 69166144(2z)-2-(3-Butyl-1,3-thiazol-2(3h)-ylidene)-1-(5-chloro-2-methoxyphenyl)ethanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred suspension of NaH (60% in mineral oil, 0.04 g, 1 mmol) in anhydrous DMF (3 mL) at 0° C. was added 5-chloro-2-methoxyacetophenone (0.15 g, 1 mmol) followed by subsequent addition of n-butylisothiocyanate (0.24 mL, 2 mmol) in DMF (3 mL). The mixture was stirred at 0° C. for 2 hours after which 2-bromo-1,1-dimethoxyethane was added. The reaction mixture was stirred for 2 hr and then poured into brine, extracted with EtOAc. The organic layer was washed with brine (3×30 mL), dried (MgSO4) and concentrated. The residue was dissolved in toluene (10 mL) then treated with p-toluenesulfonic acid (1.5 mmol) and refluxed for 6 hr. The reaction mixture was concentrated and partitioned between EtOAc and saturated NaHCO3. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography eluting with 50% ethyl acetate in hexane to provide the title compound as a yellow solid. (10 mg). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.93 (t, J=7.3 Hz, 3 H), 1.32 (dd, J=15.1, 7.3 Hz, 2 H), 1.72 (t, J=7.3 Hz, 2 H), 3.86 (s, 3 H), 4.01 (t, J=7.1 Hz, 2 H), 6.57 (s, 1 H), 6.81 (d, J=4.4 Hz, 1 H), 7.12 (d, J=8.8 Hz, 1 H), 7.33-7.48 (m, 1 H), 7.34-7.49 (m, 1 H), 7.65 (d, J=3.1 Hz, 1 H). MS (DCI), m/z 324 (M+H)+.

Workup

  1. additionwas added
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine (3×30 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in toluene (10 mL)
  7. temperaturerefluxed for 6 hr
  8. concentrationThe reaction mixture was concentrated
  9. custompartitioned between EtOAc and saturated NaHCO3
  10. washThe organic layer was washed with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customThe residue was purified by flash chromatography
  14. washeluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-1b2086c0e35f4cc19c0a3ebae8941d12
Source dataset
uspto-grants-2013_07
Patent number
US08481574B2

Linked notes

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