2,4-Dichloronitrobenzene → N-(t-butyloxycarbonyl)-4-(3-chloro-6-nitrophenoxy)-L-phenylalanine 4-pyridylamide dihydrochloride

HRID 330436

Reaction equation

HRID 330436 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:26])[C@H:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:3][CH:2]=1.[H-].[Na+].[Cl:29][C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:31]=1[N+:37]([O-:39])=[O:38]>CS(C)=O>[ClH:29].[ClH:29].[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:26])[C@H:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][C:32]3[C:31]([N+:37]([O-:39])=[O:38])=[CH:30][CH:35]=[C:34]([Cl:36])[CH:33]=3)=[CH:21][CH:20]=2)[NH:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 118992,4-DichloronitrobenzeneHCID 24758Sodium hydrideHCID 18637474N-(t-butyloxycarbonyl)-4-hydroxy-L-phenylalanine 4-pyridylamide

Product 1

HCID 18637470N-(t-butyloxycarbonyl)-4-(3-chloro-6-nitrophenoxy)-L-phenylalanine 4-pyridylamide dihydrochlorideYield 151.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of N-(t-butyloxycarbonyl)-4-hydroxy-L-phenylalanine 4-pyridylamide (5.35 g) in dimethyl sulfoxide (100 ml) was added oily sodium hydride (0.62 g), followed by stirring at room temperature for 30 minutes. Thereafter, 2,4-dichloronitrobenzene (2.88 g) was added and stirred at room temperature for 10 hours. After a conventional post-treatment, N-(t-butyloxycarbonyl)-4-(3-chloro-6-nitrophenoxy)-L-phenylalanine 4-pyridylamide dihydrochloride (6.66 g) was obtained. The above compound (I) (6.50 g) was allowed to react with 4N-hydrogen chloride/dioxane solution (50 ml) to obtain 4-(3-chloro-6-nitrophenoxy-L-phenylalanine 4-pyridylamide dihydrochloride, which was further allowed to react with trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarboxylic acid mixed acid anhydride obtained in Example 5 to obtain N-[trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarbonyl]-4-(3-chloro-6-nitrophenoxy)-L-phenylalanine 4-pyridylamide (II) (7.16 g). The above compound (II) (7.00 g) was allowed to react with 4N-hydrogenn chloride/dioxane solution (150 ml) to obtain N-(trans-4-aminomethylcyclohexylcarbonyl)-4-(3-chloro-6-nitrophenoxy)-L-phenylalanine 4-pyridylamide (6.06 g).

Workup

  1. stirringstirred at room temperature for 10 hours

Sources & evidence

ORD record
ord-ce2332cf62184218bea2b2add6f0401f
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Linked notes

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