1,3-Dichloroacetone → 2-tert-Butyl-4-(chloromethyl)-1,3-oxazole

HRID 2221677Notes

Reaction equation

HRID 2221677 reaction equation
[C:1]([NH2:7])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Cl:8][CH2:9][C:10](=O)[CH2:11]Cl.C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[C:2]([C:1]1[O:6][CH:11]=[C:10]([CH2:9][Cl:8])[N:7]=1)([CH3:5])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 107931,3-DichloroacetoneHCID 12957TrimethylacetamideHCID 516892Sodium Bicarbonate

Product 1

HCID 221695102-tert-Butyl-4-(chloromethyl)-1,3-oxazoleYield 38.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of pivalamide (30 g) and 1,3-dichloro-2-propanone (37.66 g) was stirred at 160° C. for 1.5 hrs. Saturated aqueous sodium hydrogen carbonate and ethyl acetate were added to the reaction mixture, and insoluble materials were removed by filtration. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:5-1:2, v/v). The obtained oily substance (a mixture (41 g) of 2-tert-butyl-4-chloromethyl-1,3-oxazole and 1,3-dichloro-2-propanone) was dissolved in tetrahydrofuran (500 mL) ethanol (50 mL), sodium borohydride (5 g) was added, and the mixture was stirred at room temperature for 16 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:20, v/v) to give 2-tert-butyl-4-(chloromethyl)-1,3-oxazole as a colorless oil (19.61 g, yield 38%).

Workup

  1. customwere removed by filtration
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. washeluted with ethyl acetate-hexane (1:5-1:2
  6. dissolutionThe obtained oily substance (a mixture (41 g) of 2-tert-butyl-4-chloromethyl-1,3-oxazole and 1,3-dichloro-2-propanone) was dissolved in tetrahydrofuran (500 mL) ethanol (50 mL)
  7. additionsodium borohydride (5 g) was added
  8. stirringthe mixture was stirred at room temperature for 16 hrs
  9. additionWater was poured into the reaction mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated
  14. washeluted with ethyl acetate-hexane (1:20

Sources & evidence

ORD record
ord-ee0c709b678a4d7d908cfa6cfb89c66a
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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