Triethylamine → HCID 66750899, compound

HRID 535017Notes

Reaction equation

HRID 535017 reaction equation
Cl.Cl.[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([CH3:6])([CH3:5])[CH3:4].[OH:19][C:20]1[CH:24]=[C:23]([C:25]([OH:27])=O)[O:22][N:21]=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Br[CH2:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][N:16]([C:25]([C:23]2[O:22][N:21]=[C:20]([O:19][CH2:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH:24]=2)=[O:27])[CH2:15][CH2:14]1)([CH3:6])([CH3:4])[CH3:5]

Participants

10

Reactant 7

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 79177tert-Butyl bromoacetateHCID 667511491-(2-Tert-butylphenyl)piperazine dihydrochlorideHCID 178524642HCID 178524642, compound

Product 1

HCID 66750899HCID 66750899, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (1.13 g, 3.87 mmol), 3-hydroxyisoxazole-5-carboxylic acid (0.5 g, 3.87 mmol), triethylamine (1.39 mL, 10.0 mmol), EDCI (0.959 g, 5.0 mmol) and HOBt (0.766 g, 5.0 mmol) in N,N-dimethylformamide (15 mL) was stirred at room temperature for 16 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain an oil. A mixture of the obtained oil, tert-butyl bromoacetate (0.819 g, 4.2 mmol) and potassium carbonate (0.829 g, 6.0 mmol) in N,N-dimethylformamide (10 mL) was stirred at 50° C. for 16 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to purify the residue by NH-silica gel column chromatography (hexane/ethyl acetate 90:10 to 40:60). Solvent was removed to afford oil (1.01 g, 59%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto obtain an oil
  7. stirringwas stirred at 50° C. for 16 h
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto purify the residue by NH-silica gel column chromatography (hexane/ethyl acetate 90:10 to 40:60)
  14. customSolvent was removed

Sources & evidence

ORD record
ord-852b66e75c6e4cd5a1ab95c013d31993
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

Loading…