تفاعل #62049

ord-ea7852a2269f4205a78fa8db6484b238

المذيبات

ظروف التفاعل

درجة الحرارة
0°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىthe reaction
  2. 2
    درجة الحرارةto warm to room temperature
  3. 3
    أخرىthe solvent was removed by the flow of CO2
  4. 4
    أخرىthe reaction
  5. 5
    درجة الحرارةto warm to room temperature overnight
  6. 6
    workup.ADDITIONthis mixture was poured into a separatory funnel
  7. 7
    غسيلThe organic layer was washed with brine
  8. 8
    تجفيفdried over anhydrous MgSO4
  9. 9
    ترشيحfiltered
  10. 10
    تركيزconcentrated
  11. 11
    أخرىThe crude material was further purified by flash chromatography
  12. 12
    غسيلeluting with a gradient from 100% hexanes to 25% EtOAc/hexanes

الإجراء التجريبي

To a 0.22 M solution of 2-methoxy-5,6,7,8-tetrahydroquinoline in Et2O at −78° C. was added 1.7 equiv of t-BuLi [1,7M] over 5 min. After allowing the reaction to warm up to 0° C. and stirring at this temperature for 30 min, a stream of CO2(g) was then allowed to flow into the flask. The final mixture was allowed to warm to room temperature and the solvent was removed by the flow of CO2. To a solution/suspension of the resulting crude lithium carboxylate salt in DMF (12 equiv) at 0° C. was successively added 1.2 equiv of N-[4-(dimethylamino)benzyl]4-isopropylaniline, 12 equiv of 4-methylmorpholine and 4.0 equiv of 1-propylphosphonic acid cyclic anhydride (50% in EtOAc). After allowing the reaction to warm to room temperature overnight, this mixture was poured into a separatory funnel containing aqueous NaHCO3/EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude material was further purified by flash chromatography, eluting with a gradient from 100% hexanes to 25% EtOAc/hexanes to provide the title compound as a white solid.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07429666B2uspto-grants-2008_09