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

HRID 330432Notes

Reaction equation

HRID 330432 reaction equation
C(N([CH2:6][CH3:7])CC)C.CC1C(C)CCC(N[C:17](=[O:42])[C@H:18]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]3C=CC=CC=3)=[CH:30][CH:29]=2)[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])C1.C(Cl)(=O)[O:44]CC.FC(F)(F)[C:51]1[CH:57]=[CH:56][C:54]([NH2:55])=[CH:53][CH:52]=1.O1[CH2:64][CH2:63][CH2:62][CH2:61]1>>[CH:54]1([NH:55][C:17](=[O:42])[C@H:18]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][C:36]([C:7]3[CH:6]=[CH:64][CH:63]=[CH:62][CH:61]=3)=[O:44])=[CH:32][CH:33]=2)[NH:19][C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:53][CH2:52][CH2:51][CH2:57][CH2:56]1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 99644-(Trifluoromethyl)anilineHCID 10928Ethyl chloroformateHCID 54300108N-(t-butyloxycarbonyl)-4-benzyloxy-L-phenylalanine 3,4-dimethylcyclohexylamide

Product 1

HCID 70070014N-(t-butyloxycarbonyl)-4-phenacyloxy-L-phenylalanine cyclohexylamide

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-trifluoromethylaniline (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 obtain 1.3 g of N-(t-butyloxycarbonyl)-4-benzyloxy-L-phenylalanine 4-trifluoromethylanilide (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-trifluoromethylanilide (III). On the other hand, trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarboxylic acid (0.25 g) and triethylamine (0.2 ml) were added, and ethylchlorocarbonate (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-trifluoromethylanilide (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-trifluoromethylanilide hydrochloride was obtained.

Workup

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

Sources & evidence

ORD record
ord-8a99e5996f764452a048597cce0c6f5d
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Reaction notes

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