Ethyl 1-azabicyclo(2.2.2)octane-4-carboxylate → 1-Azabicyclo[2.2.2]oct-4-yl[bis(3-methylphenyl)]methanol

HRID 1875635Notes

Reaction equation

HRID 1875635 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][CH:7]=1.[N:10]12[CH2:17][CH2:16][C:13]([C:18]([O:20]CC)=O)([CH2:14][CH2:15]1)[CH2:12][CH2:11]2>C1COCC1>[N:10]12[CH2:11][CH2:12][C:13]([C:18]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[CH:7]=3)([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[CH:7]=3)[OH:20])([CH2:14][CH2:15]1)[CH2:16][CH2:17]2

Participants

4

Reactant 2

HCID 573424Ethyl 1-azabicyclo(2.2.2)octane-4-carboxylateHCID 178425413HCID 178425413, compound

Product 1

HCID 689628891-Azabicyclo[2.2.2]oct-4-yl[bis(3-methylphenyl)]methanolYield 69.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-methylphenylmagnesiumbromide (1.0 M in THF, 3.3 mL, 3.3 mmol) was chilled down to 0° C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.1484 g, 0.810 mmol) in THF (4 mL) was slowly added to the reaction mixture at 0° C. over 20 min. The reaction was allowed to warm up to room temperature and then heated at 60° C. for 16 h. The reaction was chilled in an ice bath, quenched with saturated NH4Cl, and concentrated under vacuum. The resulting residue was treated with H2O and extracted with EtOAc. The combined organic layers were dried with MgSO4, filtered, and concentrated under vacuum to yield the desired product (0.1806 g, 69.4%). EI-MS m/z 322 (M+H+) Rt (1.54 min).

Workup

  1. temperatureheated at 60° C. for 16 h
  2. temperatureThe reaction was chilled in an ice bath
  3. customquenched with saturated NH4Cl
  4. concentrationconcentrated under vacuum
  5. additionThe resulting residue was treated with H2O
  6. extractionextracted with EtOAc
  7. dry with materialThe combined organic layers were dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4de16c29f8194e66a9777183ed92c35e
Source dataset
uspto-grants-2012_11
Patent number
US08309572B2

Reaction notes

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