Reaktion #706810

Reaktionsgleichung

ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)thiochromen-6-yl-ethynyl)-benzoate

ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thiochromen-6-ylethynyl)-benzoate

Compound 224

ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thiochromen-6-ylethynyl)-benzoate

4-bromo-2-methylpyridine

tert-butyllithium

→

title compound

Ethyl 4-[[4-(6-methyl-pyridin-3-yl)-2,2-dimethyl-(2H)-thiochromen-6-yl]-ethynyl]-benzoate

Lösungsmittel

THF

THF

pentane

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto give a red-orange solution
2. 2
   TemperaturThis solution was heated to 50° C. for 2 hours
3. 3
   Temperaturcooled to room temperature
4. 4
   Sonstigethe reaction quenched by the addition of saturated aqueous NH4Cl
5. 5
   ExtraktionThe solution was extracted with EtOAc
6. 6
   Waschenthe combined organic layers were washed with H2O and saturated aqueous NaCl
7. 7
   Trocknenbefore being dried (MgSO4)
8. 8
   Einengenconcentrated under reduced pressure

Vorschrift

A solution of 4-bromo-2-methylpyridine (220.0 mg, 1.28 mmol) in 2.0 mL of THF was cooled to -78° C. and tert-butyllithium (164.0 mg, 2.56 mmol, 1.5 ml of a 1.7M solution in pentane) was added to give a red-orange solution. After 30 minutes a solution of ZnCl2 (348.0 mg, 2.56 mmol) in 4.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature, stirred for 40 minutes, and transferred via cannula to a solution of ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)thiochromen-6-yl-ethynyl)-benzoate (Compound 224, 172.0 mg, 0.35 mmol) and tetrakis(triphenylphosphine) palladium(0) (24.0 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 2 hours, cooled to room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. The solution was extracted with EtOAc and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound, 109.0 mg (72%) was isolated by column chromatography (5% EtOAc/hexanes) as a pale-yellow solid. 1H NMR (300 MHz, CDCl3) δ: 8.45 (1H, d, J=2.0 Hz), 8.00 (2H, d, J=8.5 Hz), 7.52 (2H, d, J=8.5 Hz), 7.49 (1H, dd, J=2.3, 8.1 Hz), 7.36 (2H, m), 7.20 (1H, d, J=8.1 Hz), 7.16 (1H, d, J=1.5 Hz), 5.86 (1H, s), 4.38 (2H, q, J=7.1 Hz), 2.63 (3H, s), 1.50 (6H, s), 1.40 (3H, t, J=7.1 Hz).

Quelle