Dicyclohexylcarbodiimide → 2-{[(3r)-4-(4-Toluenesulfonyl)thiomorpholine-3-carbonyl]amino}-4-methyl-pentanoic acid ethyl ester

HRID 968522Notes

Reaction equation

HRID 968522 reaction equation
[C:1]1([CH3:19])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:15][CH2:14][S:13][CH2:12][C@H:11]2[C:16]([OH:18])=O)(=[O:9])=[O:8])=[CH:3][CH:2]=1.Cl.[CH2:21]([O:23][C:24](=[O:31])[C@H:25]([CH2:27][CH:28]([CH3:30])[CH3:29])[NH2:26])[CH3:22].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:21]([O:23][C:24](=[O:31])[CH:25]([NH:26][C:16]([C@@H:11]1[CH2:12][S:13][CH2:14][CH2:15][N:10]1[S:7]([C:4]1[CH:3]=[CH:2][C:1]([CH3:19])=[CH:6][CH:5]=1)(=[O:8])=[O:9])=[O:18])[CH2:27][CH:28]([CH3:29])[CH3:30])[CH3:22]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 11658447L-Leucine, ethyl ester, hydrochloride (1:1)HCID 69415969(3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid

Product 1

HCID 694152832-{[(3r)-4-(4-Toluenesulfonyl)thiomorpholine-3-carbonyl]amino}-4-methyl-pentanoic acid ethyl esterYield 81.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

0.301 g (1 mmol) of (3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid, 0.215 g (1.1 mmol) of L-leucine ethyl ester hydrochlorid, 0.227 g (1.2 mmol) of DCC and 0.122 g (1 mmol) of DMAP were dissolved in 30 mL of CH2Cl2, 0.2 ml (1.4 mmol) of TEA was added. The mixture was stirred for 24 h at room temperature. The solid was filtrated and the solvent was evaporated. The residual was dissolved in a suitable amount of ethyl acetate (20 ml) and then the mixture was filtered to remove insoluble substance. The ethyl acetate was added to 60 ml and then the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution and dried over Na2SO4. After the drying agent was removed and part of ethyl acetate was evaporated, the crude product was purified by flash column chromatography (eluent: CH2Cl2:CH3Cl=1:1) to obtain the product as a oil (0.36 g).

Workup

  1. filtrationThe solid was filtrated
  2. customthe solvent was evaporated
  3. dissolutionThe residual was dissolved in a suitable amount of ethyl acetate (20 ml)
  4. filtrationthe mixture was filtered
  5. customto remove insoluble substance
  6. additionThe ethyl acetate was added to 60 ml
  7. washthe liquid was washed with 10% NaHCO3 solution, saturated NaCl solution
  8. dry with materialdried over Na2SO4
  9. customAfter the drying agent was removed
  10. custompart of ethyl acetate was evaporated
  11. customthe crude product was purified by flash column chromatography (eluent: CH2Cl2:CH3Cl=1:1)

Sources & evidence

ORD record
ord-b388d4ec75094e518b2b51e90041702f
Source dataset
uspto-grants-2007_12
Patent number
US07304057B2

Reaction notes

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