Ethyl chloroformate → HCID 53735669, compound

HRID 330433Notes

Reaction equation

HRID 330433 reaction equation
C(OC(NC[C@H]1CC[C@H](C(O)=O)CC1)=O)(C)(C)C.C(OC(Cl)=O)C.C[CH:26]1[CH:31](C)[CH2:30][CH2:29][CH:28]([NH:33][C:34](=[O:69])[C@H:35]([CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH2:62][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[CH:57][CH:56]=2)[NH:36][C:37](=[O:53])[C:38]2[CH:43]=[CH:42][C:41]([CH2:44][NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])=[CH:40][CH:39]=2)[CH2:27]1>C(N(CC)CC)C>[CH:28]1([NH:33][C:34](=[O:69])[C@H:35]([CH2:54][C:55]2[CH:60]=[CH:59][C:58]([O:61][CH2:62][C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)=[CH:57][CH:56]=2)[NH:36][C:37](=[O:53])[C:38]2[CH:39]=[CH:40][C:41]([CH2:44][NH:45][C:46]([O:48][C:49]([CH3:51])([CH3:50])[CH3:52])=[O:47])=[CH:42][CH:43]=2)[CH2:29][CH2:30][CH2:31][CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 54354000HCID 54354000, compoundHCID 178453624HCID 178453624, compound

Product 1

HCID 53735669HCID 53735669, compoundYield 69.9%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent2×

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 3 hours
  3. extractionAfter extraction with chloroform

Sources & evidence

ORD record
ord-6d5155051e9d46229c9ddebbca5c2bca
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Reaction notes

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