Triethylamine → 4-[[(N-(2-amino-5-chlorobenzoyl)glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidine

HRID 1281019Notes

Reaction equation

HRID 1281019 reaction equation
[NH2:1][CH2:2][C:3]([NH:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:4].CCN(CC)CC.[NH2:27][C:28]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:29]=1[C:30](O)=[O:31].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[OH-].[Na+]>C(Cl)Cl>[NH2:27][C:28]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:29]=1[C:30]([NH:1][CH2:2][C:3]([NH:5][CH2:6][CH:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12]1)=[O:4])=[O:31]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 124762-Amino-5-chlorobenzoic acidHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11701760tert-Butyl 4-((2-aminoacetamido)methyl)piperidine-1-carboxylate

Product 1

HCID 184261834-[[(N-(2-amino-5-chlorobenzoyl)glycyl)amino]methyl]-1-(tert-butoxycarbonyl)piperidineYield 78.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-{(glycylamino}methyl)-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol) in CH2Cl2 (25 mL) was treated with Et3N (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol). After the reaction mixture was stirred at room temperature for 3 h, 2 N aqueous NaOH solution (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate) afforded the desired 4-[{(N-(2-amino-5-chlorobenzoyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (1.63 g, 78%) as a solid.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with dichloromethane (20 mL×3)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d65a8be48b9240ea8c74338ff93f77f5
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Reaction notes

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