Dicyclohexylcarbodiimide → [(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]-4-methylpentyl](phthalimidomethyl)phosphinic acid methyl ester

HRID 476693Notes

Reaction equation

HRID 476693 reaction equation
[CH3:1][O:2][P:3]([CH2:17][CH:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19](O)=[O:20])([CH2:5][N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16])=[O:4].[CH3:26][NH:27][C:28](=[O:35])[C@H:29]([CH2:31][CH:32]([CH3:34])[CH3:33])[NH2:30].O[C:37]1C2N=NNC=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[CH3:1][O:2][P:3]([CH2:17][CH:18]([C:19](=[O:20])[NH:30][C@H:29]([C:28](=[O:35])[NH:27][CH3:26])[CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:22][C:23]([CH3:37])([CH3:24])[CH3:25])([CH2:5][N:6]1[C:7](=[O:16])[C:8]2=[CH:15][CH:14]=[CH:13][CH:12]=[C:9]2[C:10]1=[O:11])=[O:4]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 11672684(2S)-2-amino-N,4-dimethylpentanamideHCID 200630192(RS)-[[(RS)-(methoxy)(phthalimidomethyl)phosphinyl]methyl]-4-methylvaleric acidHCID 178418300HCID 178418300, compound

Product 1

HCID 54363570[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]-4-methylpentyl](phthalimidomethyl)phosphinic acid methyl esterYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3.0 g of 2(RS)-[[(RS)-(methoxy)(phthalimidomethyl)phosphinyl]methyl]-4-methylvaleric acid were dissolved in 50 ml of tetrahydrofuran and 1.65 g of L-leucine N-methylamide and 2.2 g of hydroxybenzotriazole were added while stirring. After all of the solids had dissolved, 2.02 g of N,N'-dicyclohexylcarbodiimide were added and the mixture was stirred at room temperature overnight. The tetrahydrofuran was removed by evaporation, the residue was triturated with 100 ml of ethyl acetate and the mixture was filtered in order to remove dicyclohexylurea. The filtrate was washed twice with 50 ml of saturated sodium hydrogen carbonate solution each time, dried over anhydrous sodium sulfate and evaporated to give a yellow gum. This gum was purified by flash chromatography on silica gel using 5% methanol in ethyl acetate for the elution. There were obtained 3.32 g of [(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]-4-methylpentyl](phthalimidomethyl)phosphinic acid methyl ester in the form of a white foam.

Workup

  1. dissolutionAfter all of the solids had dissolved
  2. stirringthe mixture was stirred at room temperature overnight
  3. customThe tetrahydrofuran was removed by evaporation
  4. customthe residue was triturated with 100 ml of ethyl acetate
  5. filtrationthe mixture was filtered in order
  6. customto remove dicyclohexylurea
  7. washThe filtrate was washed twice with 50 ml of saturated sodium hydrogen carbonate solution each time
  8. dry with materialdried over anhydrous sodium sulfate
  9. customevaporated
  10. customto give a yellow gum
  11. customThis gum was purified by flash chromatography on silica gel using 5% methanol in ethyl acetate for the elution

Sources & evidence

ORD record
ord-cf38cf9fa7da41dea8bef27cc9ac6185
Source dataset
uspto-grants-1989_12
Patent number
US04885283

Reaction notes

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