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

HRID 1910511Notes

Reaction equation

HRID 1910511 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.[F:27][C:28]1[CH:29]=[C:30]([CH:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)O)[CH:31]=[CH:32][C:33]=1[F:34].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:35]([C:30]1[CH:31]=[CH:32][C:33]([F:34])=[C:28]([F:27])[CH:29]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:11])[CH2:3]2

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2758251(3,4-Difluorophenyl)(phenyl)methanolHCID 126734361-Azabicyclo(2.2.2)octane-3-carboxylic acid hydrochloride

Product 1

HCID 70925855(3,4-Difluorophenyl)(phenyl)methyl quinuclidine-3-carboxylateYield 43.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Quinuclidine-3-carboxylic acid hydrochloride (80 mg, 0.42 mmol), EDC (120 mg, 0.62 mmol), and HOBT (96 mg, 0.62 mmol) were dissolved in dry THF (3 ml). (3,4-Difluorophenyl)(phenyl)methanol (101 mg, 0.46 mmol) was dissolved in dry THF (2 ml) and then added to the reaction mixture. Triethylamine (203 μl, 1.46 mmol) was finally added, and the resulting reaction was stirred at room temperature overnight. The volatiles were evaporated, and the crude was taken up with EtOAc and washed with water and then with sat. NaHCO3. The organic phase was dried over sodium sulfate, filtered, and evaporated under vacuum. The crude was purified by flash chromatography (DCM/MeOH=9/1) to obtain (3,4-difluorophenyl)(phenyl)-methyl quinuclidine-3-carboxylate (65 mg, mixture of diastereoisomers).

Workup

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

Sources & evidence

ORD record
ord-c0f7c0dcb0224b5ca311e8403c7d6e60
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Reaction notes

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