Reaktion #5460

Reaktionsgleichung

dimethylsulfoxide

hydroxylamine hydrochloride

sodium methoxide methanol

sodium methoxide

1-azabicyclo[3.3.1]nonane-5-methanol

oxalyl chloride

→

colorless crystals

Ausbeute 60.0%

1-Azabicyclo[3.3.1]nonane-5-carboxaldehyde oxime

Ausbeute 60.0%

Lösungsmittel

Triethylamine

methylene chloride

methylene chloride

methylene chloride

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction temperature below -60° C
2. 2
   Sonstigethe reaction temperature below -55° C.
3. 3
   Sonstigewas kept below -50° C.
4. 4
   WaschenThe organic solution was washed with water (200 mL), saturated aqueous sodium carbonate (200 mL), and brine (200 mL)
5. 5
   Extraktioneach aqueous extract
6. 6
   TrocknenThe combined organic solution was dried (Na2SO4)
7. 7
   Einengenconcentrated in vacuo
8. 8
   workup.WAITAfter 2 hours at room temperature
9. 9
   Temperaturthe mixture was warmed to 45° C. for 30 minutes
10. 10
    Einengenpartially concentrated
11. 11
    workup.ADDITIONdiluted with methylene chloride (150 mL)
12. 12
    WaschenThe organic solution was washed with saturated aqueous sodium carbonate (100 mL)
13. 13
    Extraktionextracted with methylene chloride (3×100 mL)
14. 14
    TrocknenThe combined organic solution was dried (Na2SO4)
15. 15
    Einengenconcentrated in vacuo
16. 16
    Sonstigerecrystallized from acetonitrile (2 crops)

Vorschrift

A cooled (-65° C.) solution of oxalyl chloride (5.3 mL, 60 mmol) in anhydrous methylene chloride (100 mL) under nitrogen was treated dropwise with anhydrous dimethylsulfoxide (0.60 g, 120 mmol) in methylene chloride (30 mL) at a rate to keep the reaction temperature below -60° C. After 30 minutes at -65° C., a solution of 1-azabicyclo[3.3.1]nonane-5-methanol (6.21 g, 40 mmol) in methylene chloride (30 mL) was added dropwise at a rate to keep the reaction temperature below -55° C., and the mixture was stirred at -55°±5° C. for one hour. Triethylamine (40 mL) was added (the temperature was kept below -50° C.), then the mixture was allowed to warm to room temperature over one hour and diluted with methylene chloride (200 mL). The organic solution was washed with water (200 mL), saturated aqueous sodium carbonate (200 mL), and brine (200 mL), and each aqueous extract was backwashed with methylene chloride. The combined organic solution was dried (Na2SO4), concentrated in vacuo, and taken up in methanol (100 mL), then treated with hydroxylamine hydrochloride (3.5 g, 50 mmol) and 25% sodium methoxide/methanol (1.8 g). After 2 hours at room temperature, additional 25% sodium methoxide (9.0 g) was added, and the mixture was warmed to 45° C. for 30 minutes, then partially concentrated and diluted with methylene chloride (150 mL). The organic solution was washed with saturated aqueous sodium carbonate (100 mL), and the aqueous layer was salted with potassium carbonate and extracted with methylene chloride (3×100 mL). The combined organic solution was dried (Na2SO4), concentrated in vacuo, and recrystallized from acetonitrile (2 crops) to afford 4.03 g (60%) of colorless crystals; mp 115°-117° C.

Quelle