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

HRID 404683Notes

Reaction equation

HRID 404683 reaction equation
Cl.[F: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]([OH:12])=[O:11])=[CH:5][CH:4]=1.[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21](O)[CH2:20]2.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[F: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:21]2[CH:22]3[CH2:25][CH2:26][N:19]([CH2:24][CH2:23]3)[CH2:20]2)=[O:11])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 71432486(4-Fluorophenyl)(1-piperidinyl)acetic acid hydrochloride

Product 1

HCID 86688942(R)-quinuclidin-3-yl 2-(4-fluorophenyl)-2-(piperidin-1-yl)acetateYield 39.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(4-Fluorophenyl)-2-(piperidin-1-yl)acetic acid hydrochloride (255 mg, 0.93 mmol) was dissolved in dry THF (10 ml) and (R)-quinuclidin-3-ol (355 mg, 2.79 mmol), DCC (384 mg, 1.86 mmol), HOBt (285 mg, 1.86 mmol) were added. The mixture was stirred at room temperature for 16 hours. THF was evaporated and the residue was taken up with EtOAc and washed with sat. NaHCO3, water and brine. The organic phase was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography (DCM/MeOH/NH4OH=98/2/0.2) to obtain (R)-quinuclidin-3-yl 2-(4-fluorophenyl)-2-(piperidin-1-yl)acetate (126 mg, 39.0% yield) as a white solid.

Workup

  1. customTHF was evaporated
  2. washwashed with sat. NaHCO3, water and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude was purified by flash chromatography (DCM/MeOH/NH4OH=98/2/0.2)

Sources & evidence

ORD record
ord-548d672629464f2a9b1e4073c7bba8c3
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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