1,2-Dichloroethane → (2-Chlorophenyl)(4-chlorophenyl)methyl quinuclidine-3-carboxylate

HRID 1910510Notes

Reaction equation

HRID 1910510 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.[Cl:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH:34]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)O.C(N(CC)CC)C>C1COCC1>[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([C:10]([O:12][CH:34]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[Cl:27])[C:36]1[CH:37]=[CH:38][C:39]([Cl:42])=[CH:40][CH:41]=1)=[O:11])[CH2:3]2

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 247332(2-Chlorophenyl)(4-chlorophenyl)methanolHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride

Product 1

HCID 70925811(2-Chlorophenyl)(4-chlorophenyl)methyl quinuclidine-3-carboxylateYield 19.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Quinuclidine-3-carboxylic acid hydrochloride (0.1 g, 0.52 mmol), EDC (150 mg, 0.78 mmol), and HOBT (120 mg, 0.78 mmol) were dissolved in dry THF (3 ml). (2-Chlorophenyl)(4-chlorophenyl)methanol (145 mg, 0.57 mmol) was dissolved in dry THF (2 ml) and then added to the reaction mixture. Triethylamine (253 μl, 1.83 mmol) was added, and the resulting reaction was stirred at room temperature overnight. The mixture was evaporated, and the crude was taken up with EtOAc and washed with water and brine. The organic phase was separated, dried (sodium sulfate), filtered, and evaporated under vacuum. The crude was purified by flash chromatography (DCM/MeOH=95/5) to afford (2-chlorophenyl)(4-chlorophenyl)methyl quinuclidine-3-carboxylate (40 mg, mixture of diastereoisomers). The compound was used as such in the next step.

Workup

  1. additionadded to the reaction mixture
  2. customthe resulting reaction
  3. customThe mixture was evaporated
  4. washwashed with water and brine
  5. customThe organic phase was separated
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. customevaporated under vacuum
  9. customThe crude was purified by flash chromatography (DCM/MeOH=95/5)

Sources & evidence

ORD record
ord-eff852acc5e1415c8c3eebe1ea251ff5
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Reaction notes

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