تفاعل #710508

ord-0a7b25b44763425e9eb6dd6521348812

معادلة التفاعل

O=C(O)C12CC3CCC(CC(C3)C1)C2
Tricyclo[4.3.1.1˜3,8˜]undecane-1-carboxylic acid
Cl
HCl
[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Diphenylphosphorylazide
CCN(CC)CC
triethylamine
O=C(O)C12CC3CCC(CC(C3)C1)C2
Tricyclo[4.3.1.1˜3,8˜]undecane-1-carboxylic acid
[Cl-].[NH3+]C12CC3CCC(CC(C3)C1)C2
tricyclo[4.3.1.13,8]undecan-1-aminium chloride
المردود 75.0%

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىthe organic layer was separated
  2. 2
    غسيلwashed sequentially with H2O, saturated NaHCO3 and brine
  3. 3
    تجفيفdried over MgSO4
  4. 4
    أخرىSolvent was removed by rotary evaporation and t-BuOH (50 ml)
  5. 5
    workup.ADDITIONwas added
  6. 6
    درجة الحرارةThe solution was heated
  7. 7
    درجة الحرارةto reflux under N2 atmosphere for 5 hours
  8. 8
    أخرىExcess 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
    أخرىN2 was purged through the mixture
  11. 11
    أخرىto remove excess TFA and CH2Cl2
  12. 12
    أخرىto give yellow oil
  13. 13
    أخرىA white solid was collected by centrifugation
  14. 14
    أخرىsubsequent decanting of the ether supernatant
  15. 15
    أخرىFurther flash column chromatography purification

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US09301950B2uspto-grants-2016_04