Butyl Isothiocyanate → (z)-2-(5-Acetyl-3-butyl-4-methylthiazol-2(3h)-ylidene)-1-(5-chloro-2-methoxyphenyl)ethanone

HRID 448023

Reaction equation

HRID 448023 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].Cl[CH:23]([C:27](=[O:29])[CH3:28])[C:24](=O)[CH3:25]>CN(C=O)C.O>[C:27]([C:23]1[S:21]/[C:20](=[CH:3]\[C:4]([C:6]2[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=2[O:13][CH3:14])=[O:5])/[N:19]([CH2:15][CH2:16][CH2:17][CH3:18])[C:24]=1[CH3:25])(=[O:29])[CH3:28]

Participants

7

Reactant 4

HCID 11613Butyl IsothiocyanateHCID 24758Sodium hydrideHCID 743283-Chloro-2,4-pentanedioneHCID 2404341-(5-Chloro-2-methoxyphenyl)ethanone

Product 1

HCID 24953913(z)-2-(5-Acetyl-3-butyl-4-methylthiazol-2(3h)-ylidene)-1-(5-chloro-2-methoxyphenyl)ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of NaH (60% in mineral oil, 0.08 g, 2 mmol) in anhydrous DMF (3 mL) at 0° C. was added 5-chloro-2-methoxyacetophenone (0.37 g, 2 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 3-chloropentane-2,4-dione (0.23 mL, 2 mmol) was added drop-wise. The mixture was stirred at 0° C. for 2 hours and then heated to 90° C. for 5 hours. The mixture was cooled to ambient temperature, diluted with water (30 mL) and extracted with ethyl acetate (3×35 mL). The combined organic layers were washed sequentially with water, brine, dried with MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 50% ethyl acetate in hexane to provide the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.96 (t, J=7.3 Hz, 3 H), 1.27-1.55 (m, 2 H), 1.58-1.80 (m, 2 H), 2.45 (s, 3 H), 2.65 (s, 3 H), 3.88 (s, 3 H), 3.94-4.10 (m, 2 H), 6.78 (s, 1 H), 7.16 (d, J=8.8 Hz, 1 H), 7.47 (dd, J=8.8, 2.7 Hz, 1 H), 7.65 (d, J=2.7 Hz, 1 H). MS (DCI) m/z 380 (M+H).+ Anal calcd for C19H22ClNO3S: C, 60.07; H, 5.84; N, 3.69. Found: C, 59.56; H, 5.95; N, 3.68.

Workup

  1. additionwas added drop-wise
  2. temperatureheated to 90° C. for 5 hours
  3. temperatureThe mixture was cooled to ambient temperature
  4. extractionextracted with ethyl acetate (3×35 mL)
  5. washThe combined organic layers were washed sequentially with water, brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography
  10. washeluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-651c13ffceca4145b177a0e947f08322
Source dataset
uspto-grants-2013_07
Patent number
US08481574B2

Linked notes

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