Ethanol → HCID 66782705, compound

HRID 2095474Notes

Reaction equation

HRID 2095474 reaction equation
[H-].[Na+].C(O[C:6](=O)[CH2:7][C@@H:8]([N:10]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:11][C:12]([O:14]CC)=O)C)C.[CH2:25](O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.Cl>[CH2:17]([N:10]1[CH2:8][C@@H:7]([CH3:6])[CH2:25][C:12](=[O:14])[CH2:11]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 3

HCID 702EthanolHCID 24758Sodium hydrideHCID 11748816HCID 11748816, compound

Product 1

HCID 66782705HCID 66782705, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of sodium hydride (55% dispersion in mineral oil, 6.4 g, 14 mmol) in toluene (90 ml) was added (S)-3-(benzyl-ethoxycarbonylmethyl-amino)-butyric acid ethyl ester (20.3 g, 0.06 mol) in toluene (10 ml), followed by ethanol (1 ml). A vigorous reaction ensued, after 15 minutes the reaction was diluted with ethyl acetate, washed with 10% aq. citric acid solution, dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (ethyl acetate/heptane 1:9) affording a complex mixture of diastereomers (7.2 g, 42%). A portion of this material (3.5 g, 13 mmol) was dissolved in 25% aq. hydrochloric acid solution (20 ml) and heated in a loosely closed tube at 120° C. for 36 h. The solvent was evaporated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 1:4) afforded the titled product as a crystalline solid (1.1 g, 43%). MS (ISP)=204.3 (M+H)+.

Workup

  1. customA vigorous reaction ensued
  2. washwashed with 10% aq. citric acid solution
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (ethyl acetate/heptane 1:9)
  6. customaffording
  7. additiona complex mixture of diastereomers (7.2 g, 42%)
  8. customThe solvent was evaporated
  9. dissolutionthe residue redissolved in dichloromethane
  10. washwashed with sat. aq. sodium hydrogencarbonate solution
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customPurification by flash column chromatography (ethyl acetate/heptane 1:4)

Sources & evidence

ORD record
ord-e3bf28294f8f4f8d976c5dd114ba84ce
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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