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

HRID 1281020Notes

Reaction equation

HRID 1281020 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:22]=[CH:21][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17](=[O:20])[CH2:18][NH2:19])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.CCN(CC)CC.[C:30]([O:34][C:35]([NH:37][C:38]1[CH:46]=[C:45]([F:47])[C:44]([F:48])=[CH:43][C:39]=1[C:40](O)=[O:41])=[O:36])([CH3:33])([CH3:32])[CH3:31].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[OH-].[Na+]>C(Cl)Cl>[C:30]([O:34][C:35]([NH:37][C:38]1[CH:46]=[C:45]([F:47])[C:44]([F:48])=[CH:43][C:39]=1[C:40]([NH:19][CH2:18][C:17]([NH:16][CH2:15][CH:12]1[CH2:11][CH2:10][N:9]([CH2:8][C:7]2[CH:21]=[CH:22][C:4]([Cl:3])=[CH:5][CH:6]=2)[CH2:14][CH2:13]1)=[O:20])=[O:41])=[O:36])([CH3:33])([CH3:31])[CH3:32]

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)piperidineYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(4-chlorobenzyl)-4-{(glycylamino)methyl}piperidine dihydrochloride (738 mg, 2 mmol) in CH2Cl2 (20 mL) was treated with Et3N (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). After the reaction mixture was stirred at room temperature for 14 h, 0.6 N aqueous NaOH solution (50 mL) was added, and the mixture was extracted with dichloromethane (3 times) The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate then ethyl acetate/methanol=92/8) afforded the desired 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 mixture was extracted with dichloromethane (3 times) The combined organic layers
  2. dry with materialwere dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8eefd9f538de456aaf84da5a22b0dd82
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Reaction notes

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