1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 23282822, compound

HRID 884828Notes

Reaction equation

HRID 884828 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.C(OC([N:24]1[CH2:29][CH2:28][CH:27]([NH2:30])[CH2:26][CH2:25]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[NH2:30][CH:27]1[CH2:28][CH2:29][N:24]([C:7](=[O:9])[C:6]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)([OH:16])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:25][CH2:26]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 948620alpha-Cyclopentylmandelic acid, (+)-HCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 23282822HCID 23282822, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-cyclopentylhydroxyphenyl acetic acid (1.0 g, 4.54 mmol) in DCM (50 mL) was added t-butoxycarbonyl-4-aminopiperidine (0.9 g, 4.5 mmol). DIPEA (2.4 mL, 1.4 mmol) and HOBt (1.0 g, 6.8 mmol) were added to the mixture, followed by EDCI (1.0 g, 5.5 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was then washed with 1N NaOH (50 mL), 1N HCl (50 mL), and then saturated aqueous NaCl (50 mL). The organic layer was dried over MgSO4 and filtered. The solvent was removed by rotary evaporation. To the crude material was added a solution of 20% TFA/DCM and the reaction was stirred for 2 hours at room temperature. The solvent was removed by rotary evaporation. DCM (50 mL) was added and the mixture was then washed with saturated sodium bicarbonate (50 mL). The organic layer was removed, dried over MgSO4 and filtered. The crude material was purified by silica gel chromatography (10% MeOH/DCM with 1% NH3 (aq)) to afford the title compound as a white powder (920 mg, 3.0 mmol).

Workup

  1. washThe mixture was then washed with 1N NaOH (50 mL), 1N HCl (50 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customThe solvent was removed by rotary evaporation
  5. additionTo the crude material was added a solution of 20% TFA/DCM
  6. stirringthe reaction was stirred for 2 hours at room temperature
  7. customThe solvent was removed by rotary evaporation
  8. additionDCM (50 mL) was added
  9. washthe mixture was then washed with saturated sodium bicarbonate (50 mL)
  10. customThe organic layer was removed
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customThe crude material was purified by silica gel chromatography (10% MeOH/DCM with 1% NH3 (aq))

Sources & evidence

ORD record
ord-08ed6c10c2184dccb9b0d0456516c03a
Source dataset
uspto-grants-2012_08
Patent number
US08242138B2

Reaction notes

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