反応 #69456

反応方程式

HCl

lithium bis(trimethylsilyl)amide

methyl 3-acetyl-5-bromo-4-hydroxybenzoate

morpholine-4-carbonyl chloride

→

methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate

収率 90.2%

溶媒

THF

water

DCM

反応条件

後処理

1. 1
   温度maintained at this temperature for 1 h
2. 2
   温度The solution was cooled back to −65° C.
3. 3
   温度then cooled to −30° C.
4. 4
   抽出HCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×)
5. 5
   乾燥The combined extracts were dried over MgSO4
6. 6
   その他evaporated
7. 7
   その他The crude product was triturated in MTBE

実験手順

To a solution of lithium bis(trimethylsilyl)amide (1.41 L, 1406 mmol) at −65° C. under nitrogen was added dropwise methyl 3-acetyl-5-bromo-4-hydroxybenzoate (120 g, 439 mmol) in THF (1.2 L). The solution was allowed to warm to 0° C., and maintained at this temperature for 1 h. The solution was cooled back to −65° C. and morpholine-4-carbonyl chloride (0.055 L, 483 mmol) was added. The mixture was stirred at room temperature for 2 h then cooled to −30° C., DCM (1.5 L) and water (1 L) were added followed by dropwise addition of HCl 6N (500 mL) then HCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×). The combined extracts were dried over MgSO4 and evaporated. The crude product was triturated in MTBE to obtain methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate (153 g, 90%) as a beige solid. Mass Spectrum: m/z [M+H]+=388.

出典