تفاعل #88183

ord-3980f80b95d54813af43c984dd55e2ae

المذيبات

ظروف التفاعل

درجة الحرارة
15°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةmaintaining the temperature at 15° C
  2. 2
    درجة الحرارةThe reaction mixture was warmed to 20-25° C.
  3. 3
    تركيزThe reaction mixture was concentrated under reduced pressure
  4. 4
    أخرىthe residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL)
  5. 5
    استخلاصThe aqueous phase was further extracted with ethyl acetate (2 times with 100 mL)
  6. 6
    غسيلThe 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
    تجفيفThe organic layer was then dried over sodium sulfate
  8. 8
    ترشيحfiltered
  9. 9
    تركيزconcentrated

الإجراء التجريبي

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).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US09440949B2uspto-grants-2016_09