1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Methyl 1-{[4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetyl}piperidine-4-carboxylate

HRID 534948Notes

Reaction equation

HRID 534948 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:21])[C:18]([OH:20])=O)[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].[NH:22]1[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:23]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(=O)([O-])O.[Na+]>C(#N)C>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:12][CH2:13][N:14]([C:17](=[O:21])[C:18]([N:22]2[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:23]2)=[O:20])[CH2:15][CH2:16]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 424914Methyl isonipecotateHCID 516892Sodium BicarbonateHCID 667508542-[4-(2-Tert-butylphenyl)piperazin-1-yl]-2-oxoacetic acid

Product 1

HCID 66751159Methyl 1-{[4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetyl}piperidine-4-carboxylateYield 40.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of [4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetic acid (Example 44, 0.300 g, 1.03 mmol), methyl piperidine-4-carboxylate (0.178 g, 1.24 mmol), EDCI (0.238 g, 1.24 mmol) and HOBt (0.168 g, 1.24 mmol) in acetonitrile (10 mL) was stirred at room temperature for 2 days. The reaction mixture was poured into saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with saturated sodium hydrogen carbonate solution and brine, dried over MgSO4, and the solvent was evaporated in vacuum to give the crude product. The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=90:10 to 50:50) to provide methyl 1-{[4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetyl}piperidine-4-carboxylate (0.173 g, 40%) as a white amorphous.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated sodium hydrogen carbonate solution and brine
  3. dry with materialdried over MgSO4
  4. customthe solvent was evaporated in vacuum
  5. customto give the crude product
  6. customThe product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=90:10 to 50:50)

Sources & evidence

ORD record
ord-d0305f1ae63b4d09b7b70300ad4de134
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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