Triethylamine → 3-Chloro-2-fluoro-N-[3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-2-ylidene]-6-trifluoromethylbenzamide

HRID 78431Notes

Reaction equation

HRID 78431 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:9]([CH3:10])=[C:8]([CH3:11])[S:7][C:6]1=[NH:12].CCN(CC)CC.[Cl:20][C:21]1[C:22]([F:34])=[C:23]([C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=1)[C:24](Cl)=[O:25]>C1COCC1>[Cl:20][C:21]1[C:22]([F:34])=[C:23]([C:27]([C:30]([F:32])([F:33])[F:31])=[CH:28][CH:29]=1)[C:24]([N:12]=[C:6]1[N:5]([CH2:4][CH2:3][O:2][CH3:1])[C:9]([CH3:10])=[C:8]([CH3:11])[S:7]1)=[O:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27737843-Chloro-2-fluoro-6-(trifluoromethyl)benzoyl chlorideHCID 668517233-(2-Methoxy-ethyl)-4,5-dimethyl-3H-thiazol-2-ylideneamine

Product 1

HCID 686223863-Chloro-2-fluoro-N-[3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-2-ylidene]-6-trifluoromethylbenzamideYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of the product of Example 126A (0.20 g, 1.1 mmol) in 35 mL THF was added Et3N (0.37 mL, 2.7 mmol). This mixture was cooled to 0° C. and 3-chloro-2-fluoro-6-trifluoromethyl benzoyl chloride (Alfa Aesar, 0.35 g, 13 mmol) in 5 mL THF was added dropwise via syringe. The mixture was allowed to stir at ambient temperature for 1 hour, then was warmed to reflux and was allowed to stir for 8 hours. The mixture was then cooled to ambient temperature and filtered. The filtrate was concentrated under reduced pressure and purified via flash column chromatography (SiO2, 7:3 hexanes:EtOAc) to provide the title compound (0.20 g, 0.50 mmol, 46% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.27 (s, 3H), 2.28 (s, 3H), 3.27 (s, 3H), 3.68 (t, J=4.7 Hz, 2H), 4.28-4.37 (m, 2H), 7.37-7.43 (m, 1H), 7.44-7.52 (m, 1H); MS (DCI/NH3) m/z 411 (M+H)+; Anal. calculated for C16H15ClF4N2O2S: C, 46.78; H, 3.68; N, 6.82. Found: C, 46.83; H, 3.30; N, 6.65.

Workup

  1. temperaturewas warmed
  2. temperatureto reflux
  3. stirringto stir for 8 hours
  4. temperatureThe mixture was then cooled to ambient temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompurified via flash column chromatography (SiO2, 7:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-68dc45826a7c4026b5d45edc4d15b70b
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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