تفاعل #69456

معادلة التفاعل

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

المردود 90.2%

المذيبات

THF

water

DCM

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةmaintained at this temperature for 1 h
2. 2
   درجة الحرارةThe solution was cooled back to −65° C.
3. 3
   درجة الحرارةthen cooled to −30° C.
4. 4
   استخلاصHCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×)
5. 5
   تجفيفThe combined extracts were dried over MgSO4
6. 6
   أخرىevaporated
7. 7
   أخرىThe crude product was triturated in MTBE

الإجراء التجريبي

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.

المصدر