تفاعل #47633

ord-f4ff490e70f646ee8381e3bcaebe325b

المذيبات

ظروف التفاعل

درجة الحرارة
140°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىIn a round bottom flask was placed
  2. 2
    أخرىThis mixture was then split into two 5 mL portions
  3. 3
    أخرىplaced in two sealed microwave reaction tubes
  4. 4
    أخرىThe contents of the two reaction tubes
  5. 5
    تركيزconcentrated in vacuo
  6. 6
    workup.ADDITIONdiluted with dichloromethane (20 mL)
  7. 7
    غسيلwashed with a 1N aqueous hydrochloric acid solution (10 mL)
  8. 8
    تجفيفa saturated sodium bicarbonate solution (10 mL), dried over magnesium sulfate
  9. 9
    ترشيحfiltered
  10. 10
    تركيزconcentrated in vacuo
  11. 11
    أخرىPurification by AnaLogix IntelliFlash flash chromatography (12 g column, 15% ethyl acetate/hexanes to 30% ethyl acetate/hexanes)

الإجراء التجريبي

In a round bottom flask was placed 2-amino-3-bicyclo[2.2.1]hept-2-yl-propionic acid methyl ester (206 mg, 1.04 mmol), N,N-diisopropylethylamine (390 μL, 2.24 mmol) and 4-bromo-3-(2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 36, 390 mg, 2.24 mmol) in acetonitrile (10 mL). This mixture was then split into two 5 mL portions and placed in two sealed microwave reaction tubes and heated in a microwave reactor at 140° C. for 1 h. The contents of the two reaction tubes were combined, concentrated in vacuo and diluted with dichloromethane (20 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), a saturated sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (12 g column, 15% ethyl acetate/hexanes to 30% ethyl acetate/hexanes) afforded 3-bicyclo[2.2.1]hept-2-yl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid methyl ester (87 mg, 15%) as a yellow oil.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07741327B2uspto-grants-2010_06