Hydrochloric Acid → 5-Ethyl-4-methyl-2-p-tolyloxazole 3-oxide

HRID 2421219Notes

Reaction equation

HRID 2421219 reaction equation
[CH2:1]([C:3]([CH2:5][CH3:6])=[O:4])[CH3:2].[N:7](OCCC(C)C)=[O:8].Cl.[CH3:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1>C(OCC)C.CC(=NO)C(=O)CC.C(O)(=O)C>[CH2:1]([C:3]1[O:4][C:21]([C:20]2[CH:23]=[CH:24][C:17]([CH3:16])=[CH:18][CH:19]=2)=[N+:7]([O-:8])[C:5]=1[CH3:6])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 7288Ethyl ketoneHCID 77254-MethylbenzaldehydeHCID 8053Isoamyl Nitrite

Product 1

HCID 576829605-Ethyl-4-methyl-2-p-tolyloxazole 3-oxide

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 67974532,3-Pentanedione, 2-oximeSolvent

Procedure

Diethyl ketone is reacted with isoamyl nitrite and HCl in diethyl ether, resulting in pentane-2,3-dione 2-oxime (G. Buechi, J. Galindo, J.Org.Chem. (1991) 56(8), 2605-2606). The latter is reacted with p-methylbenzaldehyde and HCl in acetic acid to give 5-ethyl-4-methyl-2-p-tolyloxazole 3-oxide (P. M. Weintraub, J. Med. Chem. (1972) 15(4), 419-420). Boiling this compound with phosphoryl chloride in chloroform results in 4-chloromethyl-5-ethyl-2-p-tolyloxazole (M. S. Malamas, R. P. Carlson, D. Grimes, R. Howell, K. Glaser, I. Gunawan, J. A. Nelson, M. Kanzelberger, U. Shah, D. A. Hartman, J. Med. Chem. (1996) 39(1), 237-245). This compound is heated with sodium iodide in acetone under reflux, resulting in 5-ethyl-4-iodomethyl-2-p-tolyloxazole (A., Zlatkov, P., Peikov, J., Rodriguez-Alvarez, N., Danchev, I., Nikolova, J., Mitkov, Eur.J.Med.Chem.Chim.Ther. (2000) 35(10), 941-948).

Sources & evidence

ORD record
ord-b8cc668f22d64606bc8c85e15c28bd86
Source dataset
uspto-grants-2011_06
Patent number
US07956077B2

Reaction notes

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