Reacción #710508

Ecuación de reacción

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

Rendimiento 75.0%

Disolventes

dioxane

CH2Cl2

CH2Cl2

H2O

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe organic layer was separated
2. 2
   Lavadowashed sequentially with H2O, saturated NaHCO3 and brine
3. 3
   Secadodried over MgSO4
4. 4
   OtroSolvent was removed by rotary evaporation and t-BuOH (50 ml)
5. 5
   workup.ADDITIONwas added
6. 6
   TemperaturaThe solution was heated
7. 7
   Temperaturato reflux under N2 atmosphere for 5 hours
8. 8
   OtroExcess 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
    OtroN2 was purged through the mixture
11. 11
    Otroto remove excess TFA and CH2Cl2
12. 12
    Otroto give yellow oil
13. 13
    OtroA white solid was collected by centrifugation
14. 14
    Otrosubsequent decanting of the ether supernatant
15. 15
    OtroFurther flash column chromatography purification

Procedimiento

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.

Fuente