Triethylamine → 4-[[(N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl)amino]methyl]-1-(4-chlorobenzyl)piperidine

HRID 133608Notes

Reaction equation

HRID 133608 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([NH:15][C:16]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:17]=1[C:18]([OH:20])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[Cl:50][C:51]1[CH:69]=[CH:68][C:54]([CH2:55][N:56]2[CH2:61][CH2:60][CH:59]([CH2:62][NH:63][C:64](=[O:67])[CH2:65][NH2:66])[CH2:58][CH2:57]2)=[CH:53][CH:52]=1.[OH-].[Na+]>ClCCl>[C:8]([O:12][C:13]([NH:15][C:16]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:17]=1[C:18]([NH:66][CH2:65][C:64]([NH:63][CH2:62][CH:59]1[CH2:60][CH2:61][N:56]([CH2:55][C:54]2[CH:68]=[CH:69][C:51]([Cl:50])=[CH:52][CH:53]=2)[CH2:57][CH2:58]1)=[O:67])=[O:20])=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 184261442-((Tert-butoxycarbonyl)amino)-4,5-difluorobenzoic acidHCID 184261541-(4-Chlorobenzyl)-4-[(glycylamino)methyl]piperidine dihydrochloride

Product 1

HCID 184261994-[[(N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl)amino]methyl]-1-(4-chlorobenzyl)piperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (1.1 mL, 8 mmol), 2-(tert-butoxycarbonylamino)-4,5-difluorobenzoic acid (607 mg, 2.2 mmol), EDCI (422 mg, 2.2 mmol) and HOBt (337 mg, 2.2 mmol) were added to a dichloromethane (20 mL) solution of 1-(4-chlorobenzyl)-4-[(glycylamino)methyl]piperidine dihydrochloride (738 mg, 2 mmol), and the resulting mixture was stirred at room temperature for 14 hours. A 0.6 M aqueous solution of NaOH (50 mL) was then added to the mixture, and the obtained mixture was extracted with dichloromethane (3 times). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to thereby provide 4-[[(N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl) glycyl)amino]methyl]-1-(4-chlorobenzyl)piperidine (1.01 g, 92%). ESI/MS m/e 551.3 (M++H, C27H33ClF2N4O4).

Workup

  1. extractionthe obtained mixture was extracted with dichloromethane (3 times)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to thereby provide 4-[[(N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl) glycyl)amino]methyl]-1-(4-chlorobenzyl)piperidine (1.01 g, 92%)

Sources & evidence

ORD record
ord-d28599fe984941de9bac9910aa2ad906
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

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