Water → [2-(2,6-Difluorophenyl)-4,5-dihydro-1,3-oxazol-4-yl]methanol

HRID 35936Notes

Reaction equation

HRID 35936 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[C:9]=1[C:15]1[O:16][CH2:17][CH:18]([C:20](OC)=[O:21])[N:19]=1.O.[OH-].[K+]>O1CCCC1>[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[C:9]=1[C:15]1[O:16][CH2:17][CH:18]([CH2:20][OH:21])[N:19]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14797Potassium HydroxideHCID 19424096HCID 19424096, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 15375943[2-(2,6-Difluorophenyl)-4,5-dihydro-1,3-oxazol-4-yl]methanolYield 74.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of 0.58 g (15.3 mmol.) of lithium aluminum hydride and 50 ml of anhydrous tetrahydrofuran was refluxed by heating with stirring for 10 minutes. Then the mixture was cooled to a temperature of 0° C. To the mixture, there was added dropwise a solution of 4.54 g (18.8 mmol.) of 2-(2,6-difluorophenyl)-4-methoxycarbonyl-2-oxazoline obtained in Production Example 21 in 13 ml of anhydrous tetrahydrofuran with stirring at a temperature of 0° C. for 20 minutes. Then the reaction mixture was further stirred at the same temperature for 10 minutes. To the resultant mixture, there was added 0.58 ml of water with stirring at the same temperature for 5 minutes. Then the mixture was further stirred at the same temperature for 5 minutes. To the resultant mixture, there was added 0.58 ml of a 30% aqueous solution of potassium hydroxide and further 1.74 ml of water with stirring at the same temperature. After adding, the above mixture was vigorously stirred overnight at room temperature. Then, the mixture was filtrated with a filter glass to remove the resultant precipitate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography to give 3.0 g of 2-(2,6-difluorophenyl)-4-hydroxymethyl-2-oxazoline as a white solid (m.p. 90.4° C.).

Workup

  1. temperaturewas refluxed
  2. temperatureby heating
  3. stirringwith stirring at a temperature of 0° C. for 20 minutes
  4. stirringThen the reaction mixture was further stirred at the same temperature for 10 minutes
  5. stirringwith stirring at the same temperature for 5 minutes
  6. stirringThen the mixture was further stirred at the same temperature for 5 minutes
  7. stirringwith stirring at the same temperature
  8. additionAfter adding
  9. waitthe above mixture was vigorously stirred overnight at room temperature
  10. filtrationThen, the mixture was filtrated with a filter glass
  11. customto remove the resultant precipitate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ef531ba7412e47858cb19905570bd41b
Source dataset
uspto-grants-1995_05
Patent number
US05411979

Reaction notes

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