Methanol → 2-(5-Methyl-2-phenyl-4-oxazolyl)ethanol

HRID 47909Notes

Reaction equation

HRID 47909 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][C:14](OC)=[O:15].[BH4-].[Na+].CO.O>O1CCCC1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][OH:15]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 2775318Methyl (5-methyl-2-phenyl-1,3-oxazol-4-yl)acetate2×HCID 4311764Sodium borohydride

Product 1

HCID 7255852-(5-Methyl-2-phenyl-4-oxazolyl)ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 2-(5-methyl-2-phenyl-4-oxazolyl)acetate (compound [5]; 170 g) obtained in Example 2 was dissolved in tetrahydrofuran (935 mL) and sodium borohydride (27.81 g) was added at room temperature. This suspension was heated to 60° C. and stirred, and methyl alcohol (57.9 mL) was added dropwise over 1 hr. After dropwise addition, the reaction mixture was cooled to room temperature and water (35 mL) was added dropwise. The mixture was stirred at room temperature for 1 hr and filtered to remove solid components. The solid components were washed with tetrahydrofuran and the washing was combined with the previous filtrate, which was followed by concentration under reduced pressure. Ethyl acetate (1 L) was added to the residue and after dissolution, water (1 L) was added for partitioning. The aqueous layer was again extracted with ethyl acetate (0.5 L), and the organic layers were combined and washed successively with saturated sodium hydrogencarbonate solution (1 L) and saturated brine (1 L) and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give crude crystals (compound [6]; 149 g). The crystals were recrystallized from a mixed solvent of n-hexane (1 L) and ethyl acetate (0.2 L) to give the title compound (compound [6]; 134 g, yield 89.7%).

Workup

  1. additionAfter dropwise addition
  2. temperaturethe reaction mixture was cooled to room temperature
  3. stirringThe mixture was stirred at room temperature for 1 hr
  4. filtrationfiltered
  5. customto remove solid components
  6. washThe solid components were washed with tetrahydrofuran
  7. concentrationwas followed by concentration under reduced pressure
  8. additionEthyl acetate (1 L) was added to the residue
  9. dissolutionafter dissolution, water (1 L)
  10. additionwas added
  11. customfor partitioning
  12. extractionThe aqueous layer was again extracted with ethyl acetate (0.5 L)
  13. washwashed successively with saturated sodium hydrogencarbonate solution (1 L) and saturated brine (1 L)
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationAfter filtration
  16. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6fd4ae1048674da2af2797b56468f3a2
Source dataset
uspto-grants-2004_03
Patent number
US06699996B2

Reaction notes

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