1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl 4-{(2-hydroxyethyl)[(4-methyl-1H-imidazol-5-yl)carbonyl]amino}piperidine-1-carboxylate

HRID 1162337Notes

Reaction equation

HRID 1162337 reaction equation
Cl.[CH3:2][C:3]1[NH:7][CH:6]=[N:5][C:4]=1[C:8]([OH:10])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C[Si](C)(C)NC(=O)C.[OH:40][CH2:41][CH2:42][NH:43][CH:44]1[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]1>C(#N)C.C(N(CC)CC)C>[OH:40][CH2:41][CH2:42][N:43]([C:8]([C:4]1[N:5]=[CH:6][NH:7][C:3]=1[CH3:2])=[O:10])[CH:44]1[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 757711-HydroxybenzotriazoleHCID 131606155-Methyl-1H-imidazole-4-carboxylic acid hydrochloride (1:1)HCID 23131007tert-Butyl 4-(2-hydroxyethylamino)piperidine-1-carboxylate

Product 1

HCID 23138256Tert-butyl 4-{(2-hydroxyethyl)[(4-methyl-1H-imidazol-5-yl)carbonyl]amino}piperidine-1-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

5-Methylimidazole-4-carboxylic acid hydrochloride (G. Wellman et al., Synthesis, 356 (1984); 1.6 g) was suspended in acetonitrile (100 ml). HOBt (2.8 g) and WSC (3.5 g) were sequentially added thereto, and mixed at room temperature for 20 minutes (the reaction solution A). In a separate flask were dissolved tert-butyl 4-(2-hydroxyethyl)amino-1-piperidinecarboxylate (3.0 g) obtained in Example 91a), N-trimethylsilylacetamide (8.1 g) and triethylamine (5.0 ml) in acetonitrile (50 ml), and mixed at room temperature for 20 minutes (the reaction solution B). The reaction solution B was added to the reaction solution A, and mixed at room temperature for 15 hours. Acetonitrile was distilled off under reduced pressure, and then to the residue were added chloroform and water. The organic layer was collected by separation and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified with basic silica gel column (ethyl acetate:ethanol=5:1) to obtain the title compound as a colorless oil (2.0 g, 59%).

Workup

  1. additionmixed at room temperature for 15 hours
  2. distillationAcetonitrile was distilled off under reduced pressure
  3. additionto the residue were added chloroform and water
  4. customThe organic layer was collected by separation
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified with basic silica gel column (ethyl acetate:ethanol=5:1)

Sources & evidence

ORD record
ord-1a6206433765403cbe790f6a12e6176e
Source dataset
uspto-grants-2010_10
Patent number
US07820673B2

Reaction notes

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