1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-Cyclopentyl-2-hydroxy-2-phenyl-1-piperazin-1-ylethanone

HRID 1627419Notes

Reaction equation

HRID 1627419 reaction equation
[CH:1]1([C@@:6]([OH:16])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:17]1(C(OC(C)(C)C)=O)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[CH:1]1([C@@:6]([OH:16])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 948620alpha-Cyclopentylmandelic acid, (+)-

Product 1

HCID 57613502(R)-2-Cyclopentyl-2-hydroxy-2-phenyl-1-piperazin-1-ylethanoneYield 68.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-cyclopentylhydroxyphenyl acetic acid (10.0 g, 45.4 mmol) in DCM (200 mL) was added t-butyl 1-piperazinecarboxylate (8.5 g, 45.4 mmol). Into the reaction was added DIPEA (23.7 mL, 13.6 mmol), HOBt (10.4 g, 68.1 mmol), and then EDCI (10.4 g, 54.5 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was then washed with 1N NaOH (300 mL), 1N HCl (300 mL) then saturated aqueous NaCl (300 mL). The organic layer was then removed, dried over MgSO4 and then filtered. The solvent was removed under reduced pressure. A solution of 20% TFA/DCM was added to the crude material, and the resulting mixture was stirred for 2 hours at room temperature. The solvent was removed under reduced pressure. DCM (300 mL) was added and the mixture was washed with saturated sodium bicarbonate (300 mL). The organic layer was then removed, dried over MgSO4 and filtered. The crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq)) to afford the title compound as a white powder (9.0 g, 31.2 mmol).

Workup

  1. washThe mixture was then washed with 1N NaOH (300 mL), 1N HCl (300 mL)
  2. customThe organic layer was then removed
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. additionA solution of 20% TFA/DCM was added to the crude material
  7. stirringthe resulting mixture was stirred for 2 hours at room temperature
  8. customThe solvent was removed under reduced pressure
  9. additionDCM (300 mL) was added
  10. washthe mixture was washed with saturated sodium bicarbonate (300 mL)
  11. customThe organic layer was then removed
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. customThe crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq))

Sources & evidence

ORD record
ord-5f2ba401dcce4aa1b17a9a7085f9b586
Source dataset
uspto-grants-2014_07
Patent number
US08785633B2

Reaction notes

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