Dicyclohexylcarbodiimide → HCID 67199908, compound

HRID 547284Notes

Reaction equation

HRID 547284 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([C:8]1[CH:9]=[C:10]([C@@H:14]([CH3:18])[C:15]([OH:17])=O)[CH:11]=[CH:12][CH:13]=1)=[O:7].O1CCOCC1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:51][O:52][C:53](=[O:57])[CH:54]([CH3:56])[NH2:55]>CN(C=O)C.CCCCCC.C(N(CC)CC)C>[CH3:51][O:52][C:53](=[O:57])[CH:54]([NH:55][C:15](=[O:17])[C@@H:14]([C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([C:6]([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)=[O:7])[CH:9]=1)[CH3:18])[CH3:56]

Participants

9

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 2756298Alanine, methyl ester, hydrochloride (1:1)HCID 86625606HCID 86625606, compound

Product 1

HCID 67199908HCID 67199908, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of (R)-2-[3-(2-furanoyl)phenyl]propionic acid (V) (2 g, 8.2 mmol) in dioxane (5 mL) thionyl chloride (0.92 mL, 12.3 mmol) was added and the resulting solution was heated at reflux for 3 h. After cooling at room temperature the solvent was evaporated and the crude acyl chloride was dissolved in DMF (5 mL) at 0° C. and DCC (1.69 g, 8.2 mmol) and HOBT (1.01 g, 7.5 mmol) were added under stirring. After 30 min. a solution of D,L-alanine methyl ester hydrochloride (1.08 g, 7.5 mmol) and triethylamine (1.01 mL) in DMF (2 mL) was added. The resulting mixture was left stirring for 2 h at 0° C. and overnight at room temperature. The precipitated DCU was filtered off; the filtrate was diluted with EtOAc (15 mL) and the organic phase washed with 10% citric acid buffer (2×10 mL), with a saturated solution of NaHCO3 (2×10 mL) and then with brine (10 mL). After drying over Na2SO4, solvent was evaporated to give a crude that was suspended in n-hexane (20 mL) and left stirring overnight at room temperature. 2-[(R)-2-[3-(furan-2-carbonyl)phenyl]propionylamino]propionic acid methyl ester was isolated by filtration as white powder (1.66 g, 5.7 mmol). Yield 69%. To a solution of the methyl ester in dioxane (3 mL), 1N NaOH (5.7 mL) was added and the mixture left stirring overnight at room temperature. An ice/water mixture (40 mL) was added and the resulting mixture was acidified with conc. H2SO4 to pH=2. The aqueous phase was extracted with CH2Cl2 (4×15 mL) and the collected organic extracts were washed back with brine (15 mL), dried over Na2SO4 and evaporated under vacuum to give an oily residue. 37 was isolated by crystallization from ethyl ether (10 mL) as white solid (0.72 g, 2.28 mmol). Yield 40%.

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureat reflux for 3 h
  3. customwas evaporated
  4. dissolutionthe crude acyl chloride was dissolved in DMF (5 mL) at 0° C.
  5. waitThe resulting mixture was left
  6. stirringstirring for 2 h at 0° C. and overnight at room temperature
  7. filtrationThe precipitated DCU was filtered off
  8. additionthe filtrate was diluted with EtOAc (15 mL)
  9. washthe organic phase washed with 10% citric acid buffer (2×10 mL), with a saturated solution of NaHCO3 (2×10 mL)
  10. dry with materialAfter drying over Na2SO4, solvent
  11. customwas evaporated
  12. customto give a crude that
  13. waitleft
  14. stirringstirring overnight at room temperature

Sources & evidence

ORD record
ord-0d53ff673ac449bf9d11d652c1e749ec
Source dataset
uspto-grants-2011_05
Patent number
US07939521B2

Reaction notes

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