Diisopropylamine → 6'-Fluorospiro[1-azabicyclo[2.2.2]octane-3,2'(3'h)-furo[2,3-b]pyridine]

Temperatur

-78 °C

A solution of phenyllithium (1.8 M in cyclohexane, 13.5 mL) was added to THF (15 mL) under argon. Diisopropylamine (0.5 mL) was added, and the solution was cooled to −78° C. (dry ice/acetone bath temperature). To the resulting solution, 2,6-difluoropyridine (1.23 mL, 1.56 g, 13.6 mmol) was added dropwise, then after 1 h, a solution of spiro[1-azabicyclo[2.2.2]octane-3,2′-oxirane] N-borane complex (765 mg, 5.0 mmol) in tetrahydrofuran was added dropwise. The solution was stirred at −78° C. for 1 h and the cooling bath was then replaced with a dry ice/acetonitrile bath. The solution was then stirred overnight, warming to room temperature. Saturated aqueous sodium bicarbonate was added, and the solution was then extracted with chloroform. The extract was then dried (MgSO4), filtered, and evaporated. The residue was dissolved in DMF (20 mL), and was then added to a suspension of hexane-washed sodium hydride (60% mixture with mineral oil, 507 mg, 12.7 mmol) in DMF (20 mL) stirred at 0° C. The solution was stirred overnight, warming to room temperature. Saturated aqueous sodium bicarbonate was added to the solution, which was then extracted with chloroform. The extract was then dried (MgSO4), filtered, and evaporated, and the residue was purified by HPLC using a gradient of 5-50% ethyl acetate and hexane to give the sub-title compound (102 mg, 8%, 0.41 mmol): electrospray MS (m/z) 247 [M−H]+.

1. customthe cooling bath was then replaced with a dry ice/acetonitrile bath
2. stirringThe solution was then stirred overnight
3. temperaturewarming to room temperature
4. extractionthe solution was then extracted with chloroform
5. dry with materialThe extract was then dried (MgSO4)
6. filtrationfiltered
7. customevaporated
8. dissolutionThe residue was dissolved in DMF (20 mL)
9. additionwas then added to a suspension of hexane-
10. stirringstirred at 0° C
11. stirringThe solution was stirred overnight
12. temperaturewarming to room temperature
13. extractionwas then extracted with chloroform
14. dry with materialThe extract was then dried (MgSO4)
15. filtrationfiltered
16. customevaporated
17. customthe residue was purified by HPLC

ORD-Eintrag

ord-ef34ca03816647bcb9908d540df736cf

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06703502B2