Acetic Acid → (R)-Quinuclidin-3-yl 2-(4-methylbenzylamino)-2-phenylacetate

HRID 77007Notes

Reaction equation

HRID 77007 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10](=[O:19])[CH:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2]2.[CH3:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C1CCCCC1>[N:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[C@@H:3]([O:9][C:10](=[O:19])[CH:11]([NH:18][CH2:20][C:21]1[CH:28]=[CH:27][C:24]([CH3:25])=[CH:23][CH:22]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 77254-MethylbenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59401091(R)-quinuclidin-3-yl 2-amino-2-phenylacetate

Product 1

HCID 59401115(R)-Quinuclidin-3-yl 2-(4-methylbenzylamino)-2-phenylacetateYield 54.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolvent

Procedure

To a solution of amino-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (I76) (100 mg, 0.38 mmol) in dry THF (3.84 mL), are added 4-methylbenzaldehyde (68 mL, 0.57 mmol) and AcOH (0.5 mL, 8.73 mmol). The mixture is stirred at RT and sodium triacetoxyborohydride (163 mg, 0.77 mmol) is added. The reaction is stirred at RT for 1.5 hours then cyclohexane is added and the mixture is evaporated to dryness. The crude is purified by flash chromatography (DCM/MeOH/NH4OH=95/5/0.5) to obtain the title compound as a colorless oil (76 mg, 54% yield, mixture of diastereoisomers).

Workup

  1. stirringThe reaction is stirred at RT for 1.5 hours
  2. customthe mixture is evaporated to dryness
  3. customThe crude is purified by flash chromatography (DCM/MeOH/NH4OH=95/5/0.5)

Sources & evidence

ORD record
ord-74b3e9a6b35b420ca4eddb16d9a94bcb
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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