Pyridine → HCID 13343702, compound

HRID 1154597Notes

Reaction equation

HRID 1154597 reaction equation
[Cl:1][C:2]1[C:13]([C:14](=O)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2F)=[CH:12][C:5]2[CH2:6][CH:7]([C:9]([OH:11])=[O:10])[O:8][C:4]=2[C:3]=1[Cl:23].Cl.[NH2:25][OH:26].N1[CH:32]=[CH:31]C=CC=1.[OH-].[K+]>C(O)C>[O:26]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[C:14]([C:13]2[C:2]([Cl:1])=[C:3]([Cl:23])[C:4]3[O:8][CH:7]([C:9]([O:11][CH2:31][CH3:32])=[O:10])[CH2:6][C:5]=3[CH:12]=2)=[N:25]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 13343701HCID 13343701, compound

Product 1

HCID 13343702HCID 13343702, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 6,7-dichloro-2,3-dihydro-5-(2-fluorobenzoyl)benzofuran-2-carboxylic acid (15 g.) hydroxylamine hydrochloride (20 g.) and pyridine (80 ml.) was heated at reflux for 5 hours. The pyridine was evaporated under reduced pressure and the residue poured slowly into cold, 5% HCl. The resulting solid was filtered and dried to give 12 g. of the corresponding oxime. The oxime was dissolved in 100 ml. of absolute ethanol and mixed with a solution of 9.4 g. of potassium hydroxide in 150 ml. of ethanol. After refluxing for 2 hours, the solution was allowed to cool and the precipitated potassium carboxylate salt was filtered. This salt was converted to the free acid as described in Example 42 and then esterified by stirring overnight in 150 ml. of ethanol containing 0.5 ml. of concentrated H2SO4. Partial evaporation of the ethanol was followed by distribution of the residue between methylene chloride and saturated aqueous HCl. The organic phase was dried and evaporated to give a mixture of ethyl esters. The mixture was subjected to preparative high pressure liquid chromatography to afford pure samples of ethyl 8-chloro-3-(2-fluorophenyl)-5,6-dihydrofuro[3,2-f]-1,2-benzizisoxazole-6-carboxylate, m.p. 135°-136° C. and ethyl 5-(1,2-benzisoxazole-3-yl)-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylate, m.p 114°-116° C. The corresponding carboxylic acids were obtained by hydrolysis with potassium hydroxide. Thus, a 1 g. sample of each ester was dissolved in 25 ml. of 80% aqueous methanol containing 2 molar equivalents of KOH. After 2 hours at room temperature, the methanol was partially evaporated and the residue diluted with water. Acidification with hydrochloric acid furnished the acids: 8-chloro-3-(2-fluorophenyl)-5,6-dihydrofuro[3,2-f]-1,2-benzisoxazole-6-carboxylic acid, m.p. 197.5°-199° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 hours
  3. customThe pyridine was evaporated under reduced pressure
  4. additionthe residue poured slowly into cold, 5% HCl
  5. filtrationThe resulting solid was filtered
  6. customdried
  7. customto give 12 g
  8. temperatureAfter refluxing for 2 hours
  9. temperatureto cool
  10. filtrationthe precipitated potassium carboxylate salt was filtered
  11. customPartial evaporation of the ethanol
  12. customThe organic phase was dried
  13. customevaporated
  14. customto give

Sources & evidence

ORD record
ord-6a849fdcb03a4dd39ea9d5ac76e4e02b
Source dataset
uspto-grants-1984_12
Patent number
US04490384

Reaction notes

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