Triethylamine → (S)-3-{3-[3-Ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureidomethyl}-piperidine-1-carboxylic Acid Tert-butyl Ester

HRID 896559Notes

Reaction equation

HRID 896559 reaction equation
C(OC(N1CCCC(CO)C1)=O)(C)(C)C.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH2:26][C@@H:25]([CH2:29][NH2:30])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C1([O:37][C:38](=O)[NH:39][C:40]2[CH:45]=[C:44]([C:46]3[N:50]([CH3:51])[N:49]=[N:48][N:47]=3)[CH:43]=[C:42]([CH2:52][CH3:53])[CH:41]=2)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH2:26][C@@H:25]([CH2:29][NH:30][C:38]([NH:39][C:40]2[CH:45]=[C:44]([C:46]3[N:50]([CH3:51])[N:49]=[N:48][N:47]=3)[CH:43]=[C:42]([CH2:52][CH3:53])[CH:41]=2)=[O:37])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1502022tert-Butyl (3S)-3-(aminomethyl)piperidine-1-carboxylateHCID 2763851tert-Butyl 3-(hydroxymethyl)piperidine-1-carboxylateHCID 22252693Phenyl 3-ethyl-5-(1-methyl-1H-tetraazol-5-yl)phenylcarbamate

Product 1

HCID 69736969(S)-3-{3-[3-Ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureidomethyl}-piperidine-1-carboxylic Acid Tert-butyl EsterYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Racemic 3-hydroxymethylpiperidine-1-carboxylic acid tert-butyl ester was resolved using the procedure of B. Wirz and W. Walther, Tetrahedron Asymm. 1992, 3, 1049. The (R) isomer was converted into (S)-3-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester by the method of K. Hilpert et al., J. Med. Chem. 1994, 37, 3889. A solution of this material (119 mg, 556 μmol) in N,N-dimethylformamide (4 mL) was treated with [3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester (180 mg, 556 μmol) and triethylamine (155 μL, 1.11 mmol) and the mixture was stirred at room temperature for 21 hours. The mixture was concentrated under vacuum, and the residue was dissolved in dichloromethane. The solution was washed with 1.0 N aqueous sodium hydroxide, dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography, elution with 70% ethyl acetate in hexane, to provide a white glassy solid (193 mg, 78%). 1H NMR (300 MHz, CDCl3) δ7.64 (s, 1H), 7.55 (s, 1H), 7.18 (s, 1H), 4.20 (s, 3H), 3.9-3.6 (m, 3H), 3.28 (m, 1H), 3.05 (m, 2H), 1.83 (m, 1H), 2.66 (q, J=8 Hz, 2H), 1.9-1.5 (m, 5H), 1.46 (s, 9H), 1.24 (t, J=8 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washThe solution was washed with 1.0 N aqueous sodium hydroxide
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash chromatography, elution with 70% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5426fdd4cf5a4111b1a15f42f002d485
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

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