Реакция #658326

ord-524d2f7dc238422d958932f2f1cc270c

Растворители

Условия реакции

Температура
-78°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    workup.STIRRINGthe mixture was kept stirring for an additional hour at −78° C
  2. 2
    workup.STIRRINGthe white suspension was stirred at −78° C. for 20 min
  3. 3
    Температураslowly warmed to rt
  4. 4
    Другоеthe two phases were separated
  5. 5
    Экстракцияthe resulting aqueous phase was extracted with Et2O (4×)
  6. 6
    СушкаThe combined organic phase was dried (MgSO4)
  7. 7
    Фильтрацияfiltered
  8. 8
    Другоеevaporated
  9. 9
    ДругоеThe residue was purified by flash column chromatography

Методика

Oxalyl chloride (580 mg, 392 μL, 4.6 mmol) was diluted in CH2Cl2 (12 mL) under argon and the solution was cooled to −78° C. Dry DMSO (715 mg, 650 μL, 9.15 mmol) in CH2Cl2 (3 mL) was added to the cold solution dropwise and the mixture was stirred for 30 min. A solution of alcohol 23 (500 mg, 1.83 mmol) in CH2Cl2 (4 mL) was then added slowly, and the mixture was kept stirring for an additional hour at −78° C. Et3N (1.3 g, 1.8 mL, 12.8 mmol) was then introduced, the white suspension was stirred at −78° C. for 20 min and slowly warmed to rt. A 0.5 M phosphate buffer solution pH 5.5 (20 mL) was added, the two phases were separated and the resulting aqueous phase was extracted with Et2O (4×). The combined organic phase was dried (MgSO4), filtered, and evaporated. The residue was purified by flash column chromatography using hexanes/EtOAc (6:1 to 4:1) to yield the desired aldehyde 24 (433 mg, 86%) as a light yellow oil. TLC: Rf=0.76 (hexanes/EtOAc=1:1); 1H NMR (CDCl3, 300 MHz) δ 9.77 (t, J=1.3 Hz, 1H), 4.35 (m, 1H), 4.30-4.19 (m, 3H), 4.04 (dd, J=2.3, 9.8 Hz, 1H), 3.92 (ddd, J=5.3, 6.7, 9.5 Hz, 1H), 3.77 (dd, J=1.7, 10.1 Hz, 1H), 3.75 (ddd, J=5.2, 6.2, 9.5 Hz, 1H), 2.69 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 200.1, 88.3, 76.1, 71.8, 63.1, 43.7, 23.3.

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US09024038B2uspto-grants-2015_05