Hydrochloric Acid → HCID 178498871, compound

HRID 1762800Notes

Reaction equation

HRID 1762800 reaction equation
CO.[Na].CO[C:6](=O)[CH2:7][N:8](C=O)[CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1.[CH:21]([O:23][CH3:24])=[O:22].Cl.[S-:26][C:27]#[N:28].[K+]>O1CCCC1.O>[CH3:24][O:23][C:21]([C:7]1[N:8]([CH2:9][C:10]2[CH:11]=[C:12]([F:17])[CH:13]=[C:14]([F:16])[CH:15]=2)[C:27]([SH:26])=[N:28][CH:6]=1)=[O:22]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 887MethanolHCID 7865Methyl formateHCID 516872Potassium thiocyanateHCID 5360545SodiumHCID 14254152N-formyl-(3,5-difluorobenzyl)glycine methyl ester

Product 1

HCID 178498871HCID 178498871, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methanol (1.54 ml, 0.0381 mole) was added to a suspension of sodium (0.876 g, 0.0381 mole) in dry tetrahydrofuran and the mixture stirred for 30 minutes. A solution of N-formyl-N-(3,5-difluorobenzyl)-glycine methyl ester (8.50 g, 0.0349 mole) in methyl formate (6.57 ml, 0.107 mole) was added dropwise with cooling at 10° to 15° C. and the resulting mixture was stirred overnight at room temperature. The solvent was removed under vacuum and the residue was diluted with 100 ml water-methanol (1:1). The solution was treated with activated carbon, filtered, and cooled in ice. Hydrochloric acid (12N, 6.4 ml) and a solution of potassium thiocyanate (4.25 g, 0.0437 mole) in a minimum amount of water were added and the resulting solution was heated at 65°-70° C. for 24 hours. The solution was treated with activated carbon, filtered and the solvent was removed under vacuum until a precipitate formed. The mixture was cooled in ice and the product filtered and washed with a mixture of methanol-water. The product was trituarted with ethanol, filtered and dried to give a solid melting at 177°-178° C. (6.75 g, 68%).

Workup

  1. temperaturewith cooling at 10° to 15° C.
  2. stirringthe resulting mixture was stirred overnight at room temperature
  3. customThe solvent was removed under vacuum
  4. additionthe residue was diluted with 100 ml water-methanol (1:1)
  5. additionThe solution was treated with activated carbon
  6. filtrationfiltered
  7. temperaturecooled in ice
  8. temperaturethe resulting solution was heated at 65°-70° C. for 24 hours
  9. additionThe solution was treated with activated carbon
  10. filtrationfiltered
  11. customthe solvent was removed under vacuum until a precipitate
  12. customformed
  13. temperatureThe mixture was cooled in ice
  14. filtrationthe product filtered
  15. washwashed with a mixture of methanol-water
  16. filtrationfiltered
  17. customdried

Sources & evidence

ORD record
ord-f6381b26d47c42b4accaeef3b1238c29
Source dataset
uspto-grants-1989_05
Patent number
US04835154

Reaction notes

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