반응 #69456

반응 방정식

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

수율 90.2%

용매

THF

water

DCM

반응 조건

후처리

1. 1
   온도maintained at this temperature for 1 h
2. 2
   온도The solution was cooled back to −65° C.
3. 3
   온도then cooled to −30° C.
4. 4
   추출HCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×)
5. 5
   건조The combined extracts were dried over MgSO4
6. 6
   기타evaporated
7. 7
   기타The crude product was triturated in MTBE

실험 절차

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.

출처