Benzaldehyde → 4-(Chloromethyl)-5-methyl-2-phenyl-1,3-oxazole

HRID 1059090Notes

Reaction equation

HRID 1059090 reaction equation
[CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10](=[N:14]O)[C:11](=O)[CH3:12].[ClH:16].C(OC(C)C)(C)C>C(O)(=O)C>[Cl:16][CH2:9][C:10]1[N:14]=[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[O:8][C:11]=1[CH3:12]

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 313Hydrochloric Acid2×HCID 7914Diisopropyl EtherHCID 63989692-Oxime 2,3-butanedione

Product 1

HCID 97942894-(Chloromethyl)-5-methyl-2-phenyl-1,3-oxazole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Benzaldehyde (342 g) and acetic acid (800 ml) were added to 2,3-butanedione oxime (300 g), and the mixture was stirred for dissolution at room temperature, followed by cooling. Hydrochloric acid gas was started to be blown into the mixture at 5° C., and hydrochloric acid gas was continuously blown at 10-25° C. for 5 hr. Diisopropyl ether (1200 ml) was added at 10-15° C. over about 1 hr, and the mixture was aged at 5-10° C. for 1 hr. The precipitated solid was collected by filtration and washed twice with diisopropyl ether (400 ml) to give a pale-yellow white solid (not dried, 527 g) . 120 g therefrom was suspended in tetrahydrofuran (360 ml), cooled, and a solution of thionyl chloride (117 ml, 191 g) in tetrahydrofuran (240 ml) was added at 3-6° C. over about 40 min. The mixture was heated to 25° C. over about 1 hr, stirred with heating under reflux (66° C.) for 6 hr. The mixture was cooled to 27° C. over about 1 hr, and stirred under ice-cooing at 5-10° C. for 1 hr. The precipitated solid was collected by filtration and washed with tetrahydrofuran (24 ml×2) to give 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole (not dried, 119 g) as a pale-yellow white solid. Acetonitrile (57.9 ml) was added (suspended) to 23.7 g therefrom and pure water (9.7 ml) was added for dissolution at 21° C. Pure water (96.5 ml) was added at 21-24° C. over about 1 hr, and the mixture was cooled and stirred at 5-10° C. for 3 hr. The precipitated solid was collected by filtration, washed with pure water (20 ml×2) and dried under reduced pressure (40° C.) to give 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole (15.9 g) as a pale-yellow white solid in a yield of 56.7%.

Workup

  1. temperatureby cooling
  2. customto be blown into the mixture at 5° C.
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed twice with diisopropyl ether (400 ml)
  5. customto give a pale-yellow white solid (not
  6. customdried
  7. temperaturecooled
  8. additiona solution of thionyl chloride (117 ml, 191 g) in tetrahydrofuran (240 ml) was added at 3-6° C. over about 40 min
  9. temperatureThe mixture was heated to 25° C. over about 1 hr
  10. stirringstirred
  11. temperaturewith heating
  12. temperatureunder reflux (66° C.) for 6 hr
  13. temperatureThe mixture was cooled to 27° C. over about 1 hr
  14. stirringstirred under ice-cooing at 5-10° C. for 1 hr
  15. filtrationThe precipitated solid was collected by filtration
  16. washwashed with tetrahydrofuran (24 ml×2)

Sources & evidence

ORD record
ord-7d44ac369bf0436aa7833a9e4fb6b60f
Source dataset
uspto-grants-2003_02
Patent number
US06518435B1

Reaction notes

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