Water → HCID 58483030, compound

HRID 238958Notes

Reaction equation

HRID 238958 reaction equation
C([O:3][C:4](=[O:23])[CH:5]([C:20](=O)[CH3:21])[CH2:6][C:7](=O)[CH2:8][C@@H:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:10])C.[Cl:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[C:27]([CH3:32])[CH:26]=1.O>C(O)(=O)C>[Cl:24][C:25]1[CH:31]=[CH:30][C:28]([N:29]2[C:7]([CH2:8][C@@H:9]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH3:10])=[CH:6][C:5]([C:4]([OH:3])=[O:23])=[C:20]2[CH3:21])=[C:27]([CH3:32])[CH:26]=1

Participants

5

Reactant 3

HCID 962WaterHCID 72514-Chloro-2-toluidineHCID 67360478HCID 67360478, compound

Product 1

HCID 58483030HCID 58483030, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (6S)-2-acetyl-6-(benzyloxy)-4-oxoheptanoic acid ethyl ester (2.5 g, 7.8 mmol) in acetic acid (8 ml), 4-chloro-2-methylaniline (1.1 g, 7.8 mmol) was added, and the mixture was stirred at 110° C. for 15 hours. 15 ml of water was poured to the reaction mixture, and after the organic layer was extracted with diethyl ether, it was washed with 1N aqueous sodium hydroxide solution, water, a saturated aqueous ammonium chloride solution and saturated brine, and dried with sodium sulfate. The solvent was distilled off under reduced pressure and the residue was crudely purified by silica gel column chromatography. Subsequently, the product was dissolved in a 5M aqueous sodium hydroxide solution (30 mL) and methanol (40 mL), and the mixture was stirred at 100° C. for 4 hours. After the reaction, 2M hydrochloric acid (80 mL) was added under ice-cooling to neutralize it, and it was extracted with ethyl acetate. The obtained organic layer was washed with water and saturated brine and dried with sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (2.3 g, 73%).

Workup

  1. extractionafter the organic layer was extracted with diethyl ether, it
  2. washwas washed with 1N aqueous sodium hydroxide solution, water
  3. dry with materiala saturated aqueous ammonium chloride solution and saturated brine, and dried with sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was crudely purified by silica gel column chromatography
  6. dissolutionSubsequently, the product was dissolved in a 5M aqueous sodium hydroxide solution (30 mL) and methanol (40 mL)
  7. stirringthe mixture was stirred at 100° C. for 4 hours
  8. customAfter the reaction, 2M hydrochloric acid (80 mL)
  9. additionwas added under ice-
  10. temperaturecooling
  11. extractionwas extracted with ethyl acetate
  12. washThe obtained organic layer was washed with water and saturated brine
  13. dry with materialdried with sodium sulfate
  14. distillationThe solvent was distilled off under reduced pressure
  15. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8f4708a69072413d9c4941460a03b548
Source dataset
uspto-grants-2014_02
Patent number
US08642640B2

Reaction notes

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