Oxalyl chloride → HCID 54685311, compound

HRID 2293700Notes

Reaction equation

HRID 2293700 reaction equation
[C:1]1([C@H:7]([CH2:12][CH3:13])[CH2:8][C:9]([OH:11])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:14](Cl)(=[O:18])[C:15](Cl)=O>C(Cl)Cl>[CH2:12]([C@H:7]([C:8]1[C:9](=[O:11])[O:10][C:8]2[CH2:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:15]=2[C:14]=1[OH:18])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:13]

Participants

4

Reactant 2

HCID 65578Oxalyl chlorideHCID 819029HCID 819029, compound

Product 1

HCID 54685311HCID 54685311, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3[R]-Phenylvaleric acid of formula VV-3 (400 mg) is added to methylene chloride (5 mL) followed by oxalyl chloride (0.21 mL). That mixture is heated at reflux for 3 hours. The methylene chloride is removed and 1,3,5-trimethylbenzene (10 mL) is added. The solution of the acid chloride is then heated to reflux temperatures and the title product of Preparation 87 [VV-2](210 mg) and triethylamine (210 mg) (both in 1.5 mL of 1,3,5-trimethylbenzene) are added dropwise. After complete addition the reaction is heated for an addition 3 hours. The reaction is cooled to room temperature and the solid removed by filtration. The filtrate is evaporated and the resulting residue is diluted with methanol (35 mL) and 0.5N NaOH (4 mL) and that mixture stirred at room temperature overnight. The methanol is removed and water (35 mL) added. The aqueous is extracted with ether/hexane (2×35 mL) and the aqueous is acidified with 1.6N HCl at 0° C. to pH 3. That aqueous is extracted with ethyl acetate, dried and solvent removed in vacuo to yield 318.5 mg of the title product VV-5. Chromatography over silica gel (EtOAc/methylene chloride 1:8) affords 249.2 mg of the title product.

Workup

  1. temperatureThat mixture is heated
  2. temperatureat reflux for 3 hours
  3. customThe methylene chloride is removed
  4. addition1,3,5-trimethylbenzene (10 mL) is added
  5. temperatureThe solution of the acid chloride is then heated
  6. temperatureto reflux temperatures
  7. customthe title product of Preparation 87 [VV-2](210 mg) and triethylamine (210 mg) (both in 1.5 mL of 1,3,5-trimethylbenzene)
  8. additionare added dropwise
  9. additionAfter complete addition the reaction
  10. temperatureis heated for an addition 3 hours
  11. customthe solid removed by filtration
  12. customThe filtrate is evaporated
  13. additionthe resulting residue is diluted with methanol (35 mL) and 0.5N NaOH (4 mL)
  14. customThe methanol is removed
  15. additionwater (35 mL) added
  16. extractionThe aqueous is extracted with ether/hexane (2×35 mL)
  17. customaqueous is acidified with 1.6N HCl at 0° C. to pH 3
  18. extractionThat aqueous is extracted with ethyl acetate
  19. customdried
  20. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-7e9b1f76dc2b4314b97293497d8000d1
Source dataset
uspto-grants-1997_11
Patent number
US05686486

Reaction notes

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