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

HRID 404670Notes

Reaction equation

HRID 404670 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:9]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]([OH:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46](O)[CH2:45]2>C1COCC1>[F:2][C:3]1[CH:4]=[C:5]([CH:9]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]([O:12][C@@H:46]2[CH:47]3[CH2:50][CH2:51][N:44]([CH2:49][CH2:48]3)[CH2:45]2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 866889312-(3-Fluorophenyl)-2-(piperidin-1-yl)acetic acid hydrochloride

Product 1

HCID 86688932(R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetateYield 58.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(3-Fluorophenyl)-2-(piperidin-1-yl)acetic acid hydrochloride (225 mg, 0.82 mmol), DCC (339 mg, 1.64 mmol), and HOBT (252 mg, 1.64 mmol) were dissolved in dry THF (9 ml). (R)-quinuclidin-3-ol (314 mg, 2.47 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. THF was evaporated, the residue was taken up with EtOAc and washed with sat. NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography (DCM/MeOH=9/1) to obtain (R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetate (166 mg, 58.3 yield).

Workup

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

Sources & evidence

ORD record
ord-291ff4a0dc1f4a21be766bae9424807b
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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