4-Hydroxy-2,6-dimethylpyridine

Chemical Properties

Yellow to Brown Cryst

Uses

2,6-Dimethyl-4-hydroxypyridine is a useful synthetic intermediate. It is used in the synthesis of disubstituted pyridinyl-aminohydantoins as selective human BACE1 inhibitors.

Synthesis

The general procedure for the synthesis of 2,6-dimethyl-4-hydroxypyridine from dehydroacetic acid was as follows: five different batches of dehydroacetic acid (1.5 g, 8.92 mmol) were suspended in concentrated ammonia (4 mL) and placed in a microwave reactor (Discover system, 150 W, CEM Corporation, Matthews, North Carolina, USA) and microwave irradiated at 120°C for 20 min. Upon completion of the reaction, the reaction mixture was cooled and all batches were combined and subsequently evaporated to dryness to afford the target product 2,6-dimethyl-4-hydroxypyridine. The mass of the product was 5.91 g (108% yield), which was analyzed by LC/MS showing a purity of 73%. Unreacted dehydroacetic acid was present as a residual mass balance.The LC/MS retention time was 0.67 min and the mass spectrum (ES+) showed m/z 168 (M + CH3CN + H).

References

[1] Patent: WO2008/57497, 2008, A2. Location in patent: Page/Page column 252-253
[2] Patent: WO2008/57469, 2008, A1. Location in patent: Page/Page column 252-253
[3] Patent: WO2008/57468, 2008, A1. Location in patent: Page/Page column 252-253
[4] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1988, vol. 42, # 6, p. 373 - 377
[5] Chemische Berichte, 1887, vol. 20, p. 159