Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(4-methoxyphenyl)-2-(piperidin-1-yl)acetate

HRID 404677Notes

Reaction equation

HRID 404677 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]([O-:12])=[O:11])=[CH:5][CH:4]=1.[Li+].C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47](O)[CH2:46]2>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]([O:12][C@@H:47]2[CH:48]3[CH2:51][CH2:52][N:45]([CH2:50][CH2:49]3)[CH2:46]2)=[O:11])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 86688937HCID 86688937, compound

Product 1

HCID 86688938(R)-quinuclidin-3-yl 2-(4-methoxyphenyl)-2-(piperidin-1-yl)acetateYield 38.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium 2-(4-methoxyphenyl)-2-(piperidin-1-yl)acetate (384 mg, 1.50 mmol), DCC (621 mg, 3.01 mmol), and HOBT (461 mg, 3.01 mmol) were dissolved in dry THF (16 ml). (R)-quinuclidin-3-ol (574 mg, 4.51 mmol) was added and the mixture was stirred at room temperature for 16 hours. THF was evaporated and the crude was dissolved in EtOAc, washed with sat. NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography (DCM/MeOH/NH4OH=9/1/0.02) to obtain (R)-quinuclidin-3-yl 2-(4-methoxyphenyl)-2-(piperidin-1-yl)acetate (207 mg, 38.4% yield) as a colourless oil.

Workup

  1. customTHF was evaporated
  2. dissolutionthe crude was dissolved in EtOAc
  3. washwashed with sat. NaHCO3, water and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude was purified by flash chromatography (DCM/MeOH/NH4OH=9/1/0.02)

Sources & evidence

ORD record
ord-fb0c70230a7e4ec3ba4fbec9827eaa31
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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