Dicyclohexylcarbodiimide → HCID 131723506, compound

HRID 1282280Notes

Reaction equation

HRID 1282280 reaction equation
O1CCCCC1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][C@@H:14]([OH:18])[C:15]([OH:17])=O.[C:19]([C:21]1[CH:35]=[CH:34][C:24]([CH2:25][NH:26][C:27](=[O:33])[C@@H:28]2[CH2:32][CH2:31][CH2:30][NH:29]2)=[CH:23][CH:22]=1)#[N:20].ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C>[C:19]([C:21]1[CH:22]=[CH:23][C:24]([CH2:25][NH:26][C:27](=[O:33])[C@@H:28]2[CH2:32][CH2:31][CH2:30][N:29]2[C:15](=[O:17])[C@@H:14]([CH2:13][C:8]2[CH:7]=[CH:12][CH:11]=[CH:10][CH:9]=2)[OH:18])=[CH:34][CH:35]=1)#[N:20]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 15391796HCID 15391796, compoundHCID 131723507HCID 131723507, compound

Product 1

HCID 131723506HCID 131723506, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5.5 g (20.4 mmol) of o-tetrahydropyranyl-3-phenyl-D-lactic acid (WO 93/18060) were dissolved in 30 ml of DMF and, successively, 5.4 g (20.4 mmol), N-(p-cyanobenzyl)prolin-amide, 3.3 g (20.4 nmol) of N-hydroxybenzotriazole, 3.0 g DIPEA and 4.33 g (20.6 mmol) of dicyclohexylcarbodiimide were added. The mixture was left to stir at room temperature for 48 h. The precipitated urea was filtered off with suction and then the solvent was substantially removed under reduced pressure, and the residue was mixed with 50 ml of water and extracted with ethyl acetate. After washing with water, NaHCO3 solution and drying over Na2SO4, the ethyl acetate was distilled off, the remaining oily residue was dissolved in methanol, and the pH was. adjusted to 2 with p-toluenesulfonic acid. This solution was left to stand at room temperature for 6 h. The methanol was then distilled off, and the residue was taken up in ethyl acetate and washed with water, 5% strength citric acid and NaBCO3 solutions. The residue obtained after drying over Na2SO4 and removal of the solvent by distillation was purified by column chromatography (eluent: methylene chloride/acetone/methanol, 45/5/2). 2.5 g of white crystals were obtained, and these melted at 108° C.-110° C. after crystallization from an ether/hexane mixture.

Workup

  1. waitThe mixture was left
  2. filtrationThe precipitated urea was filtered off with suction
  3. customthe solvent was substantially removed under reduced pressure
  4. additionthe residue was mixed with 50 ml of water
  5. extractionextracted with ethyl acetate
  6. washAfter washing with water, NaHCO3 solution
  7. dry with materialdrying over Na2SO4
  8. distillationthe ethyl acetate was distilled off
  9. dissolutionthe remaining oily residue was dissolved in methanol
  10. waitThis solution was left
  11. waitto stand at room temperature for 6 h
  12. distillationThe methanol was then distilled off
  13. washwashed with water, 5% strength citric acid and NaBCO3 solutions
  14. customThe residue obtained
  15. dry with materialafter drying over Na2SO4 and removal of the solvent by distillation
  16. customwas purified by column chromatography (eluent: methylene chloride/acetone/methanol, 45/5/2)

Sources & evidence

ORD record
ord-4c8ef2ce762a4d98a5bc0b504456b5c0
Source dataset
uspto-grants-2002_09
Patent number
US06455671B1

Reaction notes

Loading…