Triethylamine → 4-[(glycylamino)methyl]-1-[4-(N-phenylcarbamoyl)benzyl]piperidine

HRID 133594Notes

Reaction equation

HRID 133594 reaction equation
[C:1]1([NH:7][C:8]([C:10]2[CH:17]=[CH:16][C:13]([CH2:14]Cl)=[CH:12][CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C2C(COC([NH:35][CH2:36][C:37]([NH:39][CH2:40][CH:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)=[O:38])=O)C3C(=CC=CC=3)C=2C=CC=1.C(N(CC)CC)C>C(#N)C>[NH2:35][CH2:36][C:37]([NH:39][CH2:40][CH:41]1[CH2:42][CH2:43][N:44]([CH2:14][C:13]2[CH:16]=[CH:17][C:10]([C:8](=[O:9])[NH:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:11][CH:12]=2)[CH2:45][CH2:46]1)=[O:38]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 114139054-(chloromethyl)-N-phenylbenzamideHCID 543594714-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine

Product 1

HCID 184262284-[(glycylamino)methyl]-1-[4-(N-phenylcarbamoyl)benzyl]piperidineYield 30.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

An acetonitrile (100 mL) solution of 4-(N-phenylcarbamoyl)benzyl chloride (800 mg, 3.26 mmol) was dropped into a mixture of 4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (1.27 g, 2.96 mmol) with triethylamine (1.25 mL, 8.88 mmol), KI (50 mg, 0.30 mmol) and acetonitrile (200 mL). The resulting mixture was stirred at room temperature for 19 hours and stirred at 60° C. for another 5 hours. After concentrating, the obtained crude product was purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96) to provide 4-[(glycylamino)methyl]-1-[4-(N-phenylcarbamoyl)benzyl]piperidine (340 mg, 30%).

Workup

  1. stirringstirred at 60° C. for another 5 hours
  2. concentrationAfter concentrating
  3. customthe obtained crude product
  4. customwas purified by column chromatography (SiO2, 5% methanol/dichloromethane-triethylamine/methanol/dichloromethane=2:2:96)

Sources & evidence

ORD record
ord-0f213beb0cf7442493f52ba91697ded6
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

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