1,2-Dichloroethane → (4-Methoxyphenyl)(phenyl)methyl quinuclidine-3-carboxylate

HRID 1910508

Reaction equation

HRID 1910508 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([C:10]([OH:12])=[O:11])[CH2:3]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)O)=[CH:31][CH:30]=1>C1COCC1>[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([C:10]([O:12][CH:35]([C:32]1[CH:31]=[CH:30][C:29]([O:28][CH3:27])=[CH:34][CH:33]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:11])[CH2:3]2

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 953754-Methoxybenzhydryl alcoholHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride

Product 1

HCID 70925768(4-Methoxyphenyl)(phenyl)methyl quinuclidine-3-carboxylateYield 13.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Quinuclidine-3-carboxylic acid hydrochloride (150 mg, 0.78 mmol), EDC (225 mg, 1.17 mmol), and HOBT (180 mg, 1.17 mmol) were dissolved in dry THF (7.5 ml). (4-Methoxyphenyl)(phenyl)methanol (184 mg, 0.86 mmol) and TEA (382 μl, 2.74 mmol) were added, and the resulting reaction was stirred at room temperature for four days. THF was removed under vacuum, and the crude residue was partitioned between EtOAc and water. The organic phase was washed with a sat. NaHCO3, dried over Na2SO4, filtered, and evaporated. The crude was purified by flash chromatography (EtOAc/MeOH=8/2 to EtOAc/MeOH=7:3+1% NH4OH) to give (4-methoxyphenyl)(phenyl)methyl quinuclidine-3-carboxylate (37 mg, mixture of diastereoisomers). The compound was used as such in the next step.

Workup

  1. customthe resulting reaction
  2. customTHF was removed under vacuum
  3. customthe crude residue was partitioned between EtOAc and water
  4. washThe organic phase was washed with a sat. NaHCO3
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude was purified by flash chromatography (EtOAc/MeOH=8/2 to EtOAc/MeOH=7:3+1% NH4OH)

Sources & evidence

ORD record
ord-f12da307f3d648fdbe9611e0ce06f43c
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Linked notes

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