反応 #85054

反応方程式

ammonium chloride

tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate

tetrahydrofuran-3-carbaldehyde

→

tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-hydroxy-3-(tetrahydrofuran-3-yl)propanoate

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   workup.STIRRINGthe mixture was stirred at −70° C. for 90 min
2. 2
   温度The reaction mixture was warmed to −20° C.
3. 3
   その他After phase separation
4. 4
   抽出the aqueous phase was extracted with diethyl ether
5. 5
   洗浄The combined organic phases were washed with saturated aqueous sodium chloride solution
6. 6
   乾燥dried (sodium sulphate)
7. 7
   ろ過filtered
8. 8
   濃縮concentrated under reduced pressure
9. 9
   その他dried
10. 10
    その他The crude product was purified by flash chromatography (KP-SIL, petroleum ether/ethyl acetate 33-75%)

実験手順

At −70° C., 6.94 ml (6.94 mmol, 1.3 eq.) of bis(trimethylsilyl)lithium amide (1M in THF) were added dropwise to a solution of 2.00 g (5.34 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate in 50 ml of tetrahydrofuran, the mixture was stirred at −70° C. for 10 min, a solution of 801 mg (8.00 mmol, 1.5 eq.) of tetrahydrofuran-3-carbaldehyde in 4 ml of tetrahydrofuran was added and the mixture was stirred at −70° C. for 90 min. The reaction mixture was warmed to −20° C., and 25 ml of semisaturated aqueous ammonium chloride solution were added. After phase separation, the aqueous phase was extracted with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered, concentrated under reduced pressure and dried. The crude product was purified by flash chromatography (KP-SIL, petroleum ether/ethyl acetate 33-75%). Yield: 1.49 g (56% of theory)

出典