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

HRID 404614Notes

Reaction equation

HRID 404614 reaction equation
Cl.[C:2]1([CH:8]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]([OH:11])=[O:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:43]12[CH2:50][CH2:49][CH:46]([CH2:47][CH2:48]1)[C@@H:45](O)[CH2:44]2>C1COCC1>[C:2]1([CH:8]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]([O:11][C@@H:45]2[CH:46]3[CH2:49][CH2:50][N:43]([CH2:48][CH2:47]3)[CH2:44]2)=[O:10])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 161894372-Phenyl-2-(piperidin-1-yl)acetic acid hydrochloride

Product 1

HCID 71603247(R)-quinuclidin-3-yl 2-phenyl-2-(piperidin-1-yl)acetateYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Phenyl-2-(piperidin-1-yl)acetic acid hydrochloride (0.87 g, 3.40 mmol) was suspended in dry THF (34.0 ml) and, while stirring at room temperature, DCC (1.40 g, 6.80 mmol), HOBT (1.04 g, 6.80 mmol) and (R)-quinuclidin-3-ol (1.30 g, 10.21 mmol) were sequentially added. The white suspension was stirred at the same temperature overnight (UPLC-MS: complete conversion). THF was evaporated and the residue was taken up with EtOAc (30 ml) and washed with water (20 ml) and then with a sat. NaHCO3 (20 ml). The organic phase was dried over Na2SO4, filtered was evaporated. The crude was purified by flash chromatography (DCM/MeOH/NH4OH=98/2/0.2 to 97/3/0.3) to obtain (R)-quinuclidin-3-yl 2-phenyl-2-(piperidin-1-yl)acetate (40 mg, 40% yield) as a colorless oil.

Workup

  1. stirringThe white suspension was stirred at the same temperature overnight (UPLC-MS: complete conversion)
  2. customTHF was evaporated
  3. washwashed with water (20 ml)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. customwas evaporated
  7. customThe crude was purified by flash chromatography (DCM/MeOH/NH4OH=98/2/0.2 to 97/3/0.3)

Sources & evidence

ORD record
ord-2601bf565b5f4cebb2c370e8966ff9c9
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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