Реакция #88183

Уравнение реакции

HOBT

methyl 3-(aminomethyl)benzoate hydrochloride

N-Methyl morpholine

(R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid

EDCl

→

(R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate

Выход 74.5%

Растворители

DMSO

THF

Условия реакции

Обработка

1. 1
   Температураmaintaining the temperature at 15° C
2. 2
   ТемператураThe reaction mixture was warmed to 20-25° C.
3. 3
   КонцентрированиеThe reaction mixture was concentrated under reduced pressure
4. 4
   Другоеthe residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL)
5. 5
   ЭкстракцияThe aqueous phase was further extracted with ethyl acetate (2 times with 100 mL)
6. 6
   ПромывкаThe combined organic extracts were rinsed sequentially with water (200 mL), saturated aqueous sodium bicarbonate solution (2 times with 100 mL), and brine (2 times with 25 mL)
7. 7
   СушкаThe organic layer was then dried over sodium sulfate
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated

Методика

To a 500-mL 3-neck flask was added methyl 3-(aminomethyl)benzoate hydrochloride (12.9 g, 64.1 mmol) followed by DMSO (26 mL). The solution was cooled to 15° C. N-Methyl morpholine (27 mL, 240 mmol) was added followed by EDCl (13 g, 68 mmol) and HOBT (4.09 g, 30 mmol), maintaining the temperature at 15° C. A solution of (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid (20.94 g, 60.98 mmol) in THF (100 mL) was added dropwise over 10 min. The reaction mixture was warmed to 20-25° C. and stirred for 4 hours. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL). The aqueous phase was further extracted with ethyl acetate (2 times with 100 mL). The combined organic extracts were rinsed sequentially with water (200 mL), saturated aqueous sodium bicarbonate solution (2 times with 100 mL), and brine (2 times with 25 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated to afford (R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate (22.3 g). MS (ES+) 491.3 (M+H).

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