Reaction #497728

Reaction equation

ethyl 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylate

Eaton's Reagent

sodium bicarbonate

→

ethyl 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-cyclohex-3-ene-1-carboxylate

Yield 83.1%

Conditions

Workup

1. 1
   TemperatureThe reaction was cooled
2. 2
   Extractionthe aqueous solution was extracted three times with ethyl acetate
3. 3
   OtherThe combined organics were dried under reduced pressure
4. 4
   Otherpurified by silica gel chromatography

Procedure

To a flask containing ethyl 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylate (Example 32, 0.18 g, 0.345 mmol) was added Eaton's Reagent (1.3 mL) and the mixture was heated at 60° C. for 2 hours. The reaction was cooled and added dropwise to saturated sodium bicarbonate. After stirring for 2 minutes, the aqueous solution was extracted three times with ethyl acetate. The combined organics were dried under reduced pressure and purified by silica gel chromatography to yield ethyl 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-cyclohex-3-ene-1-carboxylate (0.14 g, 82% yield). MS ESI: [M+H]+ m/z 489.1. 1H NMR (500 MHz, CDCl3) δ 8.65 (d, J=5.2, 1H), 7.96-7.79 (m, 2H), 7.46 (s, 1H), 7.26 (s, 1H), 7.14-6.95 (m, 2H), 6.65 (s, 1H), 4.28-3.96 (m, 2H), 2.90-2.75 (m, 1H), 2.75-2.60 (m, 1H), 2.62-2.47 (m, 3H), 2.39 (s, 3H), 2.26-2.10 (m, 1H), 1.95-1.70 (m, 1H), 1.39-1.17 (m, 3H). rhSYK activity=++

Source