反応 #710508

反応方程式

Tricyclo[4.3.1.1˜3,8˜]undecane-1-carboxylic acid

HCl

Diphenylphosphorylazide

triethylamine

Tricyclo[4.3.1.1˜3,8˜]undecane-1-carboxylic acid

→

tricyclo[4.3.1.13,8]undecan-1-aminium chloride

収率 75.0%

溶媒

dioxane

CH2Cl2

CH2Cl2

H2O

diethyl ether

反応条件

後処理

1. 1
   その他the organic layer was separated
2. 2
   洗浄washed sequentially with H2O, saturated NaHCO3 and brine
3. 3
   乾燥dried over MgSO4
4. 4
   その他Solvent was removed by rotary evaporation and t-BuOH (50 ml)
5. 5
   workup.ADDITIONwas added
6. 6
   温度The solution was heated
7. 7
   温度to reflux under N2 atmosphere for 5 hours
8. 8
   その他Excess t-BuOH was removed in vacuo
9. 9
   workup.ADDITIONthe residue was treated with 50% TFA/CH2Cl2 at ambient temperature for 2 hours
10. 10
    その他N2 was purged through the mixture
11. 11
    その他to remove excess TFA and CH2Cl2
12. 12
    その他to give yellow oil
13. 13
    その他A white solid was collected by centrifugation
14. 14
    その他subsequent decanting of the ether supernatant
15. 15
    その他Further flash column chromatography purification

実験手順

Compound S2 (tricyclo[4.3.1.13,8]undecan-1-aminium chloride) was synthesized from Tricyclo[4.3.1.1˜3,8˜]undecane-1-carboxylic acid (Matrix Scientific Cat. No. #037551) using curtius rearrangement according to the procedure described in previous report. (Nasr, K., Pannier, N., Frangioni, J. V. & Maison, W. Rigid multivalent scaffolds based on adamantane. J. Org. Chem. 73, 1056-1060 (2008). Diphenylphosphorylazide (DPPA) (1.29 ml, 6 mmol) and triethylamine (0.84 ml, 6 mmol) were added to a solution of Tricyclo[4.3.1.1˜3,8˜]undecane-1-carboxylic acid (0.97 g, 5 mmol) in 10 ml CH2Cl2 at ambient temperature. The reaction was stirred for 2 hours. An additional 10 ml CH2Cl2 and 10 ml H2O were added to the reaction mixture, the organic layer was separated and washed sequentially with H2O, saturated NaHCO3 and brine and dried over MgSO4. Solvent was removed by rotary evaporation and t-BuOH (50 ml) was added. The solution was heated to reflux under N2 atmosphere for 5 hours. Excess t-BuOH was removed in vacuo and the residue was treated with 50% TFA/CH2Cl2 at ambient temperature for 2 hours. N2 was purged through the mixture to remove excess TFA and CH2Cl2 to give yellow oil. 4M HCl in dioxane (3 ml) was added and the mixture was added dropwise to cold diethyl ether. A white solid was collected by centrifugation and subsequent decanting of the ether supernatant. Further flash column chromatography purification gave tricyclo[4.3.1.13,8]undecan-1-aminium chloride (compound S2) as a white solid (0.76 g, Yield: 75%). 1H-NMR (360 MHz, CD3OD) δ 2.28-2.24 (m, 3H), 1.96-1.93 (m, 4H), 1.90-1.87 (m, 4H), 1.82-1.72 (m, 4H), 1.55-1.52 (m, 2H); 13C-NMR (90 MHz, CD3OD) δ 53.91, 43.16, 42.46, 40.72, 38.18, 37.36, 35.87, 33.76, 32.54, 30.98, 28.38; ESI-MS: Calculated for C11H19N (M+H)+ 166.3. Found: 166.3.

出典