反応 #5460

反応方程式

dimethylsulfoxide

hydroxylamine hydrochloride

sodium methoxide methanol

sodium methoxide

1-azabicyclo[3.3.1]nonane-5-methanol

oxalyl chloride

→

colorless crystals

収率 60.0%

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

収率 60.0%

溶媒

Triethylamine

methylene chloride

methylene chloride

methylene chloride

methylene chloride

反応条件

後処理

1. 1
   その他the reaction temperature below -60° C
2. 2
   その他the reaction temperature below -55° C.
3. 3
   その他was kept below -50° C.
4. 4
   洗浄The organic solution was washed with water (200 mL), saturated aqueous sodium carbonate (200 mL), and brine (200 mL)
5. 5
   抽出each aqueous extract
6. 6
   乾燥The combined organic solution was dried (Na2SO4)
7. 7
   濃縮concentrated in vacuo
8. 8
   workup.WAITAfter 2 hours at room temperature
9. 9
   温度the mixture was warmed to 45° C. for 30 minutes
10. 10
    濃縮partially concentrated
11. 11
    workup.ADDITIONdiluted with methylene chloride (150 mL)
12. 12
    洗浄The organic solution was washed with saturated aqueous sodium carbonate (100 mL)
13. 13
    抽出extracted with methylene chloride (3×100 mL)
14. 14
    乾燥The combined organic solution was dried (Na2SO4)
15. 15
    濃縮concentrated in vacuo
16. 16
    その他recrystallized from acetonitrile (2 crops)

実験手順

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.

出典