تفاعل #2468014

ord-8174f2491ed74e569bf384045e9f3188

معادلة التفاعل

O=S([O-])O.[Na+]
sodium bisulphite
Fc1ccc(F)nc1
2,5-difluoropyridine
[Li][CH2]CCC
n-BuLi
CC(C)NC(C)C
diisopropylamine
II
iodine
Fc1cc(I)c(F)cn1
title compound
المردود 48.7%
Fc1cc(I)c(F)cn1
2,5-Difluoro-4-iodopyridine
المردود 48.7%

ظروف التفاعل

درجة الحرارة
-20°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةit was cooled to −78° C
  2. 2
    workup.STIRRINGthe mixture was stirred at −78° C. for 4 hours
  3. 3
    workup.STIRRINGthe mixture was stirred at −78° C. for 1 hour
  4. 4
    درجة الحرارةto raise until room temperature
  5. 5
    أخرىThe organic layer was separated
  6. 6
    استخلاصthe aqueous layer was extracted with diethyl ether (3×50 mL)
  7. 7
    غسيلthe combined organic layers were washed with brine
  8. 8
    تجفيفdried over anhydrous magnesium sulphate
  9. 9
    أخرىthe solvent removed under reduced pressure
  10. 10
    أخرىThe residue was purified by silica flash chromatography (5% diethyl ether in hexanes)

الإجراء التجريبي

n-BuLi 2.5M in hexanes (4.9 mL, 12.25 mmol) was added to a solution of diisopropylamine (1.7 mL, 12.20 mmol) in tetrahydrofuran (22 mL) at −20° C., under nitrogen atmosphere, over a period of 10 minutes. The solution was stirred at −20° C. for 30 min and then it was cooled to −78° C. A solution of 2,5-difluoropyridine (1.33 g, 11.5 mmol) in tetrahydrofuran (3 mL) was added over a period of 30 min and the mixture was stirred at −78° C. for 4 hours. After this time, a solution of iodine (3.20 g, 12.6 mmol) in tetrahydrofuran (10 mL) was added dropwise and the mixture was stirred at −78° C. for 1 hour. Water (1 mL) and tetrahydrofuran (3 mL) were added and the temperature was allowed to raise until room temperature, then water (25 mL) and aqueous sodium bisulphite 40% p/v (3 mL) were added. The organic layer was separated and the aqueous layer was extracted with diethyl ether (3×50 mL), the combined organic layers were washed with brine, dried over anhydrous magnesium sulphate and the solvent removed under reduced pressure. The residue was purified by silica flash chromatography (5% diethyl ether in hexanes) to yield the title compound (1.35 g, 48%) as a white crystalline solid.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08258122B2uspto-grants-2012_09