Triethylamine → t-butyloxycarbonyl-4-hydroxy-L-phenylalanine cyclohexylamide

HRID 330426Notes

Reaction equation

HRID 330426 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:20]([OH:22])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([N+]([O-])=O)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C([O:32]C(Cl)=O)C.C([C:44]1[CH:50]=[CH:49][C:47]([NH2:48])=[CH:46][CH:45]=1)(=O)C1C=CC=CC=1>O1CCCC1>[CH:47]1([NH:48][C:20](=[O:22])[C@H:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([OH:32])=[CH:15][CH:16]=2)[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:49][CH2:50][CH2:44][CH2:45][CH2:46]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 143464-AminobenzophenoneHCID 1180712-tert-Butoxycarbonylamino-3-(4-nitro-phenyl)-propionic acid

Product 1

HCID 131716286t-butyloxycarbonyl-4-hydroxy-L-phenylalanine cyclohexylamideYield 88.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-(t-butyloxycarbonyl)-4-nitro-D,L-phenylalanine (0.95 g) and triethylamine (0.4 ml) were dissolved in dry tetrahydrofuran (15 ml), and ethylchorocarbonate (0.33 g) was added under ice-cooling to the resultant solution, followed by stirring for 20 minutes. 4-benzoylaniline (0.6 g) was added to the solution and the mixture was further stirred at room temperature for 12 hours. According to a conventional post-treatment, 0.98 g of N-(t-butyloxycarbonyl)-4-nitro-D,L-phenylalanine 4-benzoylanilide (I) was obtained. To the above compound (I) (0.37 g) was added 4N-hydrogen chloride/dioxane solution (1.5 ml) and the mixture was stirred at room temperature for 1 hour. The solid precipitated by addition of ethyl ether (10 ml) into this solution was collected by filtration to give 0.33 g of 4-nitro-D,L-phenylalanine 4-benzoylanilide hydrochloride (II). Trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarboxylic acid (0.2 g) and triethylamine (0.2 ml) were dissolved in dry tetrahydrofuran (15 ml) and ethyl chlorocarbonate (0.09 g) was added to the solution under ice-cooling, followed by stirring for 20 minutes. To this solution was added the above compound (II) (0.33 g) and the mixture as stirred at room temperature for 12 hours. According to a conventional post-treatment, 0.29 g of N-[trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarbonyl]-4-nitro-D,L-phenylalanine 4-benzoylanilide (III) was obtained. The above compound (III) (0.29 g) was dissolved in 4N-hydrogen chloride/dioxane solution (1 ml), the solution was stirred at room temperature for 1 hour and then ether (8 ml) was added. The crystalline substance precipitated was collected by filtration and subjected to a conventional post-treatment, whereby 0.24 g of N-(trans-4-aminomethylcyclohexylcarbonyl)-4-nitro-D,L-phenylalanine 4-benzoylanilide hydrochloride was obtained.

Workup

  1. stirringthe mixture was further stirred at room temperature for 12 hours

Sources & evidence

ORD record
ord-bae09ce166274aed920ffa97cba60d2e
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Reaction notes

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