Реакция #12058

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Растворители

Условия реакции

Температура
0°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    workup.STIRRINGstirred at room temperature for 3 h
  2. 2
    workup.ADDITIONwas added
  3. 3
    Другоеthe reaction mixture was sealed
  4. 4
    workup.STIRRINGshaken at 60° C. for 48 h
  5. 5
    ТемператураThe reaction mixture was cooled
  6. 6
    workup.STIRRINGthe mixture was shaken at room temperature for 1 h
  7. 7
    Фильтрацияthen filtered through a PTFE frit
  8. 8
    ДругоеThe filtrate was evaporated
  9. 9
    Другоеthe crude product purified by reverse phase preparative HPLC (Prep Nova-Pak HR

Методика

A mixture of 6-hydroxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (0.02 g, 0.063 mmol) and DCM (1 mL) was cooled to 0° C. and carbonyl diimidazole (0.010 g, 0.063 mmol) was added, the mixture was stirred at 0° C. for 2 h and stirred at room temperature for 3 h. A mixture of pyrrolidine (10 mL, 0.13 mmol) and DCM (1 mL) was added and the reaction mixture was sealed and shaken at 60° C. for 48 h. The reaction mixture was cooled and water (2 mL) added, the mixture was shaken at room temperature for 1 h then filtered through a PTFE frit. The filtrate was evaporated and the crude product purified by reverse phase preparative HPLC (Prep Nova-Pak HR C18 6 μm 60 Å 30 mm×300 mm column, UV detection at 254 nm, mobile phase 95:5 methanol:water and 10 mmol ammonium acetate, gradient 50 methanol to 100% 0 to 10 min then 100% methanol to 13 min) to afford the title compound (0.16 g, 61% yield) as a pale yellow oil: m/z 417.07 (MH+); HPLC (50% to 80% gradient [95:5 MeOH:water, 10 mmol ammonium acetate] 255 nm XTERRA 2.0 ml/min) 4.20 min, 99.3%.

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US07098337B2uspto-grants-2006_08