Diisopropylethylamine → N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanyl-piperidineacetic acid methyl ester

HRID 361764Notes

Reaction equation

HRID 361764 reaction equation
[C:1]([NH:8][CH:9]([CH2:16][CH2:17][CH2:18][CH3:19])[C:10]([CH3:15])([CH3:14])[C:11]([OH:13])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=N[C:30]2[CH:31]=[CH:32][CH:33]=[N:34][C:29]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH3:53][O:54][C:55](=[O:63])[CH2:56]C1CCNCC1>ClCCl>[CH3:53][O:54][C:55](=[O:63])[CH2:56][N:34]1[CH2:29][CH2:30][CH2:31][CH2:32][CH:33]1[C:11](=[O:13])[C:10]([CH3:15])([CH3:14])[CH:9]([CH2:16][CH2:17][CH2:18][CH3:19])[NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1515259Methyl 4-piperidineacetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10778649N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanine

Product 1

HCID 86753677N-Boc-beta-n-butyl-alpha,alpha-dimethyl-beta-alanyl-piperidineacetic acid methyl esterYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-Boc-β-n-butyl-α,α-dimethyl-β-alanine (1.68 g, 6.13 mmol) in dichloromethane (30 ml) was added HATU reagent (2.8 g, 7.37 mmol) and di-i-propylethylamine (6.58 ml, 36.8 mmol) under cooling with ice. After being stirred for 30 min, to the reaction mixture was added 4-piperidineacetic acid methyl ester (1.45 g, 9.19 mmol) and stirred overnight at room temperature. After the solvent was distilled off, the resulting residue was dissolved into ethyl acetate and washed with 5% aqueous citric acid, 5% aqueous sodium bicarbonate, and brine for three times respectively. The organic layer was dried over anhydrous sodium sulfate. After the solvent was distilled off, the residue was subjected to the silica gel column chromatography (2.2×20 cm) and eluted with hexane:ethyl acetate=2:1 to give powder of N-Boc-β-n-butyl-α,α-dimethyl-β-alanyl-piperidineacetic acid methyl ester (1.70 g, 67.2%).

Workup

  1. temperatureunder cooling with ice
  2. stirringstirred overnight at room temperature
  3. distillationAfter the solvent was distilled off
  4. dissolutionthe resulting residue was dissolved into ethyl acetate
  5. washwashed with 5% aqueous citric acid, 5% aqueous sodium bicarbonate, and brine for three times respectively
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. distillationAfter the solvent was distilled off
  8. washeluted with hexane

Sources & evidence

ORD record
ord-15722305dc634e5eaa0c39234a891436
Source dataset
uspto-grants-1999_02
Patent number
US05866592

Reaction notes

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