Triethylamine → HCID 66750881, compound

HRID 534929Notes

Reaction equation

HRID 534929 reaction equation
Cl.Cl.[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[C:6]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:5]=1.[CH2:20]([O:22][C:23](=[O:28])[CH2:24][C:25](O)=[O:26])[CH3:21].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(#N)C>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:25](=[O:26])[CH2:24][C:23]([O:22][CH2:20][CH3:21])=[O:28])[CH2:12][CH2:11]2)=[C:6]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:5]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70615Monoethyl malonateHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 66751142Piperazine, 1-[4-bromo-2-(1,1-dimethylethyl)phenyl]-, hydrochloride (1:2)

Product 1

HCID 66750881HCID 66750881, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 1-(4-bromo-2-tert-butylphenyl)piperazine dihydrochloride (Reference Example 9, 0.300 g, 0.81 mmol), 3-ethoxy-3-oxopropanoic acid (0.128 g, 0.97 mmol), EDCI (0.186 g, 0.972 mmol), HOBt (0.131 g, 0.972 mmol) and triethylamine (339 4.05 mmol) in acetonitrile (10 mL) was stirred at room temperature for 16 h. 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 under reduced pressure to give the crude product. The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=80:20 to 50:50) to provide ethyl 3-[4-(4-bromo-2-tert-butylphenyl)piperazin-1-yl]-3-oxopropanoate (0.308 g, 93%) as a white solid.

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 under reduced pressure
  5. customto give the crude product
  6. customThe product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=80:20 to 50:50)

Sources & evidence

ORD record
ord-ac8546e8df9a409f8b772fd3c2835cd8
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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