Oxalyl chloride → HCID 54737114, compound

HRID 2293701Notes

Reaction equation

HRID 2293701 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 819027HCID 819027, compound

Product 1

HCID 54737114HCID 54737114, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3[S]-Phenylvaleric acid of formula WW-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 WW-2 (same as 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 additional 7 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 mixtured 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 287.0 mg of the title product. Chromatography over silica gel (EtOAc/methylene chloride 1:8) affords 199.4 mg of the title product WW-5.

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. additionWW-2 (same as VV-2) (210 mg) and triethylamine (210 mg) (both in 1.5 mL of 1,3,5-trimethylbenzene) are added dropwise
  8. additionAfter complete addition the reaction
  9. temperatureis heated for an additional 7 hours
  10. customthe solid removed by filtration
  11. customThe filtrate is evaporated
  12. additionthe resulting residue is diluted with methanol (35 mL) and 0.5N NaOH (4 mL)
  13. customThe methanol is removed
  14. additionwater (35 mL) added
  15. extractionThe aqueous is extracted with ether/hexane (2×35 mL)
  16. customaqueous is acidified with 1.6N HCl at 0° C. to pH 3
  17. extractionThat aqueous is extracted with ethyl acetate
  18. customdried
  19. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-d17d38e6de024bc7b9ce6726b1da5dab
Source dataset
uspto-grants-1997_11
Patent number
US05686486

Reaction notes

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