Реакция #508398

ord-9586b5fa2bc941efbf75a1d8e241cee3

Уравнение реакции

[Na+].[OH-]
NaOH
CC(C)(C)[Si](C)(C)OC[C@@H]1NCCN2CCC[C@@H]12
cis-1-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrrolo[1,2-a]pyrazine
Cc1cc(F)ccc1-c1cc(Cl)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide
Cc1cc(F)ccc1-c1cc(N2CCN3CCC[C@H]3[C@@H]2CO[Si](C)(C)C(C)(C)C)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
desired compound
Выход 9.7%
Cc1cc(F)ccc1-c1cc(N2CCN3CCC[C@H]3[C@@H]2CO[Si](C)(C)C(C)(C)C)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
cis-2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-[1-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide
Выход 9.7%

Растворители

Условия реакции

Температура
90°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    ДругоеThe resulting mixture was degassed by two freeze-thaw cycles
  2. 2
    Другоеto reach rt under a nitrogen atmosphere
  3. 3
    Температураto cool down to rt
  4. 4
    workup.ADDITIONdiluted with ethyl acetate (1 mL)
  5. 5
    Промывкаwashed with a saturated solution of NaHCO3 (1 mL)
  6. 6
    ЭкстракцияThe aqueous phase was extracted with ethyl acetate (3×2.5 mL)
  7. 7
    ДругоеThe combined organic extracts were dried
  8. 8
    Концентрированиеconcentrated in vacuo to a residue which
  9. 9
    Другоеwas purified by flash chromatography (Cycl/EtOAc 1:1)

Методика

To a solution of cis-1-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrrolo[1,2-a]pyrazine (D73, 50 mg) in dry toluene (0.5 mL), a solution of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (75 mg) in dry toluene (0.5 mL) was added at rt. Hexadecyltrimethylammonium chloride (25% aqueous solution, 132 microL), bis(tri-tert-butyl phosphine) palladium (19 mg) and NaOH (50% aqueous solution, 245 microL) were added. The resulting mixture was degassed by two freeze-thaw cycles and allowed to reach rt under a nitrogen atmosphere. The mixture was then heated at 90° C. for 5 hours. The mixture was allowed to cool down to rt, diluted with ethyl acetate (1 mL) and washed with a saturated solution of NaHCO3 (1 mL). The aqueous phase was extracted with ethyl acetate (3×2.5 mL). The combined organic extracts were dried and concentrated in vacuo to a residue which was purified by flash chromatography (Cycl/EtOAc 1:1) to give the desired compound (10.5 mg) as yellow oil.

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US08097618B2uspto-grants-2012_01