Dicyclohexylcarbodiimide → HCID 118193044, compound

HRID 2199530Notes

Reaction equation

HRID 2199530 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])[C@@H: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 118193044HCID 118193044, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

6 ml (0.042 mol) of TEA was added to a mixture of 4.2 g (0.14 mol) of (3R)-4-(Toluene-4-sulfonyl)-thiomorpholine-3-carboxylic acid, 3.0 g (0.017 mol) of L-leucine ethyl ester hydrochloride, 3.2 g (0.014 mol) of DCC, and 1.7 g (0.014 mol) of DMAP in 200 ml of CH2Cl2, and the mixture was reacted at room temperature for 24 h. After the reaction, the solid was removed by sucking filtration, the solvent was removed by evaporation, the residue was dissolved with an appropriate amount of ethyl acetate, filtered to remove the insoluble matter, diluted with ethyl acetate, successively washed with 10% of NaHCO3 solution and saturated NaCl solution, dried with Na2SO4. The drying agent was removed, ethyl acetate was removed by evaporation, the residue was separated by flash chromatographic column (eluent: CH2Cl2:CH3Cl=1:1), to obtain 4.0 g of oily matter. 1H-NMR (400 MHz, CDCl3): δ 7.77237-7.74077 (m, 2H), 7.36382 (d, 2H, J=7.988 Hz), 6.74090 (d, 1H, J=9.244 Hz), 4.80098-4.77466 (m, 1H), 4.68244-4.58898 (m, 1H), 4.28174-4.15708 (m, 3H), 3.53789-3.28674 (m, 1H), 3.13092 (d, 1H, J=13.676), 2.56954-2.42247 (m, 5H), 2.24620-2.20545 (m, 1H), 1.66352-1.53450 (m, 3H), 1.30702-1.26745 (m, 3H), 0.96159-0.91891 (m, 6H); MS (EI) m/z: 443.1, 397.1, 369.1, 287.1, 256.0, 213.1, 155.0, 139.0, 112.0, 91.0, 65.0.

Workup

  1. customthe mixture was reacted at room temperature for 24 h
  2. customAfter the reaction
  3. customthe solid was removed
  4. filtrationfiltration
  5. customthe solvent was removed by evaporation
  6. dissolutionthe residue was dissolved with an appropriate amount of ethyl acetate
  7. filtrationfiltered
  8. customto remove the insoluble matter
  9. additiondiluted with ethyl acetate
  10. washsuccessively washed with 10% of NaHCO3 solution and saturated NaCl solution
  11. dry with materialdried with Na2SO4
  12. customThe drying agent was removed
  13. customethyl acetate was removed by evaporation
  14. customthe residue was separated by flash chromatographic column (eluent: CH2Cl2:CH3Cl=1:1)
  15. customto obtain 4.0 g of oily matter

Sources & evidence

ORD record
ord-8cca436042f54bf482a3ce5ae068483a
Source dataset
uspto-grants-2016_06
Patent number
US09359314B2

Reaction notes

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