Reaction #165705

Reaction equation

product

N-(5-acetyl-4-methylthiazol-2-yl)-5-chloro-2-methoxybenzamide

(bromomethyl)cyclobutane

potassium t-butoxide

→

title compound

(Z)—N-(5-acetyl-3-(cyclobutylmethyl)-4-methylthiazol-2(3H)-ylidene)-5-chloro-2-methoxybenzamide

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled to ambient temperature
2. 2
   Otherquenched with 5 mL of saturated aqueous NH4Cl
3. 3
   workup.ADDITIONdiluted with 10 mL of ethyl acetate
4. 4
   OtherThe layers were separated
5. 5
   Extractionthe aqueous phase was extracted twice with 7 mL of ethyl acetate
6. 6
   DryingThe combined organic extracts were dried over anhydrous Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherPurification via column chromatography (SiO2, 40% hexanes in ethyl acetate)

Procedure

A mixture of the product of Example 238A (0.75 g, 2.3 mmol), (bromomethyl)cyclobutane (0.31 mL, 2.8 mmol), and potassium t-butoxide (0.41 g, 3.5 mmol) in 7 mL N,N-dimethylformamide was warmed to 65° C. and stirred for 16 hours. The mixture was cooled to ambient temperature, quenched with 5 mL of saturated aqueous NH4Cl and diluted with 10 mL of ethyl acetate. The layers were separated and the aqueous phase was extracted twice with 7 mL of ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification via column chromatography (SiO2, 40% hexanes in ethyl acetate) afforded the title compound. 1H NMR (300 MHz, CD3OD) δ ppm 1.88-2.15 (m, 6H), 2.51 (s, 3H), 2.75 (s, 3H), 2.83-2.96 (m, 1H), 3.89 (s, 3H), 4.46 (d, J=7.5 Hz, 2H), 7.11 (d, J=9.2 Hz, 1H), 7.45 (dd, J=8.8, 2.7 Hz, 1H), 7.99 (d, J=3.1 Hz, 1H); MS (DCI/NH3) m/z 393 (M+H)+. Anal. Calculated for C19H21ClN2O3S: C, 58.08; H, 5.39; N, 7.13. Found: C, 58.06; H, 5.20; N, 7.06.

Source