Water → HCID 21960044, compound

HRID 1459964Notes

Reaction equation

HRID 1459964 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([CH:12]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13]1)=[N:10][OH:11].[OH-].[K+].O.[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31]>C(O)C>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[F:8][C:6]1[CH:5]=[CH:4][C:3]2[C:9]([CH:12]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13]3)=[N:10][O:11][C:2]=2[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 444972Fumaric AcidHCID 73856697(2,4-Difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime

Product 1

HCID 21960044HCID 21960044, compoundYield 74.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

A mixture of (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime (10.8 g, 34.2 mmol), potassium hydroxide (10 g), water (100 ml), and ethanol (100 ml) was heated at reflux for 2 hours. At the end of the reaction, the solution was cooled and ethanol was removed on a rotary evaporator. The aqueous mixture was diluted with water (100 ml) then extracted with dichloromethane (500 ml). The organic solution was washed with brine and dried over anhydrous MgSO4. The solution was concentrated to an oil (9.8 g). The crude product was purified by flash chromatography over a silica gel column. The product thus obtained weighed 4.46 g (44%) as a light yellow oil. The oily product was dissolved in ethanol, and then treated with a solution of fumaric acid (1.73 g, 1.0 eq) in ethanol. Crystallization took place slowly with the addition of isopropyl ether. Recrystallization from ethanol (15 ml) gave 4.6 g of 6-fluoro-3-[1-(phenylmethyl)-3-pyrrolidinyl]-1,2-benzisoxazole fumarate as white crystals, m.p.=142°-144° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customAt the end of the reaction
  4. temperaturethe solution was cooled
  5. customethanol was removed on a rotary evaporator
  6. additionThe aqueous mixture was diluted with water (100 ml)
  7. extractionthen extracted with dichloromethane (500 ml)
  8. washThe organic solution was washed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. concentrationThe solution was concentrated to an oil (9.8 g)
  11. customThe crude product was purified by flash chromatography over a silica gel column
  12. customThe product thus obtained
  13. customCrystallization
  14. additionslowly with the addition of isopropyl ether
  15. customRecrystallization from ethanol (15 ml)

Sources & evidence

ORD record
ord-90f7e8078bc742bfa5b6918f95f4a3d2
Source dataset
uspto-grants-1998_12
Patent number
US05854263

Reaction notes

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