Phenacyl bromide → N-(t-butyloxycarbonyl)-4-phenacyloxy-L-phenylalanine cyclohexylamide

HRID 330425Notes

Reaction equation

HRID 330425 reaction equation
[CH:1]1([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])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH2:29](Br)[C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:31]>CN(C)C=O>[CH:1]1([NH:7][C:8](=[O:26])[C@H:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:29][C:30]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:31])=[CH:21][CH:20]=2)[NH:10][C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6259Phenacyl bromideHCID 24758Sodium hydrideHCID 131716286t-butyloxycarbonyl-4-hydroxy-L-phenylalanine cyclohexylamide

Product 1

HCID 70070014N-(t-butyloxycarbonyl)-4-phenacyloxy-L-phenylalanine cyclohexylamideYield 85.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of N-(t-butyloxycarbonyl)-4-benzyloxy-L-phenylalanine cyclohexylamide (0.68 g) obtained in Example 4, palladium black (0.10 g), cyclohexene (4 ml), and ethanol (20 ml) was allowed to react under reflux of ethanol for one hour, while stirring. After cooling, the solid was filtered off and the filtrate was concentrated under reduced pressure to obtain N-(t-butyloxycarbonyl-4-hydroxy-L-phenylalanine cyclohexylamide (I) (0.54 g). The compound (I) (0.54 g) was dissolved, without purification, in N,N-dimethylformamide (10 ml), followed by adding sodium hydride (0.06 g) thereto. The mixture was stirred at room temperature for 30 minutes. To this solution was added a solution of phenacyl bromide (0.30 g) in N,N-dimethylformamide (5 ml). The reaction was carried out at room temperature for 4 hours, followed by adding ice-water thereto. The resultant oily product was extracted with ethyl acetate. After a conventional post-treatment, N-(t-butyloxycarbonyl)-4-phenacyloxy-L-phenylalanine cyclohexylamide (II) (0.61 g) was obtained. From the compound (II), N-(trans-4-aminomethylcyclohexylcarbonyl)-4-phenacyloxy-L-phenylalanine cyclohexylamide hydrochloride (0.38 g) was obtained, following the procedure of Example 7.

Workup

  1. waitThe reaction was carried out at room temperature for 4 hours
  2. extractionThe resultant oily product was extracted with ethyl acetate

Sources & evidence

ORD record
ord-1cc822d415fd4d8190a05f4b6d2c5427
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Reaction notes

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