Triethylamine → N-(tert-butoxycarbonyl)-3-chloro-L-alanyl-L-phenylalanyl-L-leucine ethyl ester

HRID 477701Notes

Reaction equation

HRID 477701 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11](=[O:29])[C@H:12]([CH2:25][CH:26]([CH3:28])[CH3:27])[NH:13][C:14](=[O:24])[C@H:15]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[NH2:16])[CH3:9].C(N(CC)CC)C.[C:37]([O:41][C:42]([NH:44][C@H:45]([C:48](O)=[O:49])[CH2:46][Cl:47])=[O:43])([CH3:40])([CH3:39])[CH3:38].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)(Cl)Cl.CCCCCC.C(OCC)(=O)C>[CH2:8]([O:10][C:11](=[O:29])[C@H:12]([CH2:25][CH:26]([CH3:28])[CH3:27])[NH:13][C:14](=[O:24])[C@H:15]([CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[NH:16][C:48](=[O:49])[C@H:45]([CH2:46][Cl:47])[NH:44][C:42]([O:41][C:37]([CH3:38])([CH3:40])[CH3:39])=[O:43])[CH3:9]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 7020770Boc-beta-chloro-ala-ohHCID 67716275L-phenylalanyl-L-leucine ethyl ester trifluoroacetate

Product 1

HCID 15021150N-(tert-butoxycarbonyl)-3-chloro-L-alanyl-L-phenylalanyl-L-leucine ethyl esterYield 71.7%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.42 g (1 mmol) of L-phenylalanyl-L-leucine ethyl ester trifluoroacetate, 0.14 mL (1 mmol) of triethylamine and 0.26 g (1 mmol) of N-(tert-butoxycarbonyl)-3-chloro-L-alanine in 8 mL of chloroform, 0.21 g (1 mmol) of dicyclohexylcarbodiimide was added at 0° C. The resultant reaction mixture was stirred overnight at room temperature. The precipitate which formed was removed by filtration and the filtrate was washed successively with 0.5 N hydrochloric acid, water, 3% aqueous sodium bicarbonate and water, then dried over anhydrous sodium sulfate. Removal of the solvent afforded a white solid, which was mixed with 4 mL of a 1:1 mixture of ethyl acetate and n-hexane. Insoluble materials were removed by filtration and the filtrate was evaporated. The residue was recrystallized from a mixture of ethyl acetate and n-hexane to give 0.367 g (66.5%) of the desired product. The product, which has the structural formula ##STR75## melted at about 110° C. Its identity was further confirmed by IR and NMR analyses and by thin layer chromatography (Rf =0.34 in 5:1 chloroform/ethyl acetate).

Workup

  1. customThe resultant reaction mixture
  2. customThe precipitate which formed
  3. customwas removed by filtration
  4. washthe filtrate was washed successively with 0.5 N hydrochloric acid, water, 3% aqueous sodium bicarbonate and water
  5. dry with materialdried over anhydrous sodium sulfate
  6. customRemoval of the solvent
  7. customafforded a white solid, which
  8. customInsoluble materials were removed by filtration
  9. customthe filtrate was evaporated
  10. customThe residue was recrystallized from a mixture of ethyl acetate and n-hexane

Sources & evidence

ORD record
ord-ecfca5de00db48d1adac4715f32b6a8e
Source dataset
uspto-grants-1989_12
Patent number
US04888427

Reaction notes

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