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

HRID 330428Notes

Reaction equation

HRID 330428 reaction equation
C(N(CC)CC)C.[CH:8]1([NH:14][C:15](=[O:33])[C@H:16]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)[NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.C(Cl)(=O)[O:35][CH2:36][CH3:37].S([C:44]1[CH:50]=[CH:49][C:47](N)=[CH:46][CH:45]=1)(=O)(=O)N>O1CCCC1>[CH:8]1([NH:14][C:15](=[O:33])[C@H:16]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:37][C:36]([C:44]3[CH:50]=[CH:49][CH:47]=[CH:46][CH:45]=3)=[O:35])=[CH:28][CH:27]=2)[NH:17][C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 5333SulfanilamideHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 131716286t-butyloxycarbonyl-4-hydroxy-L-phenylalanine cyclohexylamide

Product 1

HCID 70070014N-(t-butyloxycarbonyl)-4-phenacyloxy-L-phenylalanine cyclohexylamideYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (1.5 ml) was added to a solution of N-(t-butyloxycarbonyl)-4-benzyloxy-L-phenylalanine (I) (2 g) dissolved in dry tetrahydrofuran (30 ml) and ethyl chlorocarbonate (0.65 g) was added under ice-cooling, followed by stirring for 30 minutes. To this solution was added 4-sulfamoylaniline (0.65 g) and the mixture was stirred at room temperature for 10 hours. Post-treatment was carried out in the same manner as in Example 1 to give 1.3 g of N-(t-butyloxycarbonyl)-4-benzyloxy-L-phenylalanine 4-sulfamoylanilide (II). To the above compound (II) (0.5 g) was added under ice-cooling 4N-hydrogen chloride/dioxane solution (3 ml) and the mixture was stirred at room temperature for 30 minutes. Post-treatment conducted in the same manner as in Example 1 gave quantitatively 4-benzyloxy-L-phenylalanine 4-sulfamoylanilide hydrochloride (III). On the other hand, trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarboxylic acid (0.25 g) and triethylamine (0.2 ml) were added, and ethyl chlorocarbonate (0.1 g) was added under ice-cooling, followed by stirring for 30 minutes. To this solution were added the above compound (III) (0.42 g) and triethylamine (1 ml), and the mixture was stirred at room temperature for 3 hours. After extraction with chloroform, according to the same post-treatment as in Example 1, 0.28 g of N-[trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarbonyl]-4-benzyloxy-L-phenylalanine 4-sulfamoylanilide (IV) was obtained. To the above compound (IV) (0.28 g) was added 4N-hydrogen chloride/dioxane solution (2 ml) and, after stirring at room temperature for 30 minutes, following the same procedure as in Example 1, 0.15 g of N-(trans-4-aminomethylcyclohexylcarbonyl)-4-benzyloxy-L-phenylalanine 4-sulfamoylanilide hydrochloride was obtained.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 10 hours

Sources & evidence

ORD record
ord-4c1a3db83db24e9485bb48fb84625b5a
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Reaction notes

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