Acetic Acid → 3-(Cyclopropylmethyl)-3-azaspiro[5,5]undecane

HRID 1042243

Reaction equation

HRID 1042243 reaction equation
[CH2:1]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][NH:3][CH2:2]1.[CH:12]1([CH:15]=O)[CH2:14][CH2:13]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>ClC(Cl)C>[CH:12]1([CH2:15][N:3]2[CH2:4][CH2:5][C:6]3([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]3)[CH2:1][CH2:2]2)[CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 4174123-Azaspiro(5.5)undecane hydrochlorideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 441853723-(Cyclopropylmethyl)-3-azaspiro[5,5]undecaneYield 94%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 3-azaspiro[5,5]undecane (0.34 g, 2.2 mmol), cyclopropanecarbaldehyde (0.14 g, 2 mmol) and NaBH(OAc)3 (0.64 g, 3 mmol) in dichloroethane (10 mL) were added AcOH (0.12 mL, 2 mmol), the resulting suspension was stirred overnight, quenched with NaHCO3 and extracted with CH2Cl2 twice, the combined organic layer was washed with brine, and dried with MgSO4. The solution was filtered, concentrated in vacuo and purified by flash chromatography. The compound was converted to the hydrochloride by passing HCl gas into the ether solution of 3-(cyclopropylmethyl)-3-azoniaspiro[5,5]undecane at 0° C., followed by decanting the ether supernatant, the final white solid (0.39 g, 80% yield) was dried in vacuo. 1H NMR (360 MHz, CDCl3) δ 2.45 (t, J=5.66 Hz, 4H), 2.23 (d, J=6.51 Hz 2H), 1.49 (t, J=5.66 Hz, 4H), 1.48-1.40 (m, 6H), 1.38-1.30 (m, 4H), 0.92-0.82 (m, 1H), 0.52-0.47 (m, 2H), 0.11-0.17 (m, 2H); 13C NMR (90 MHz, CDCl3) δ 64.55, 49.67, 36.47, 35.46, 31.00, 27.12, 21.73, 8.74, 4.19; ESI-MS: Calculated for C14H25N (M+H)+ 208.4, Found: 208.4.

Workup

  1. customquenched with NaHCO3
  2. extractionextracted with CH2Cl2 twice
  3. washthe combined organic layer was washed with brine
  4. dry with materialdried with MgSO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography
  8. customat 0° C.
  9. customby decanting the ether supernatant

Sources & evidence

ORD record
ord-e0f2b1f1d79144b2aea112e119feb9ce
Source dataset
uspto-grants-2013_10
Patent number
US08557836B2

Linked notes

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