(2-Methylbenzo[d]oxazol-6-yl)Methanol

Uses

2-Methyl-6-benzoxazolemethanol is used in the preparation of thiazolones which are useful for inhibiting the activity and function of PI3 kinases.

Synthesis

General procedure for the synthesis of (2-methylbenzo[d]oxazol-6-yl)methanol from methyl 2-methylbenzo[d]oxazole-6-carboxylate: to a solution of methyl 2-methylbenzo[d]oxazole-6-carboxylate (25 g, 0.13 mol) in tetrahydrofuran (THF, 500 mL) was slowly added lithium aluminum hydride (LiAlH4, 4.81 g, at -20 °C. 130 mL, 1 M THF solution, 0.13 mol, 1 equiv). The reaction mixture was gradually warmed to room temperature and stirred overnight. Upon completion of the reaction, the reaction was quenched by the careful addition of water (5 mL), followed by the addition of 1M sodium hydroxide (NaOH) solution (5 mL), then water (15 mL), and continued stirring for 15 minutes at room temperature. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure and purified by column chromatography (eluent ratio of 1:3 ethyl acetate:dichloromethane) to afford 12.5 g of the target product (2-methylbenzo[d]oxazol-6-yl)methanol in 58% yield. The product was confirmed by 1H-NMR (CDCl3): δ 2.64 (s, 3H), 4.82 (s, 2H), 7.29 (d, 1H, J=8Hz), 7.53 (s, 1H), 7.62 (d, 1H, J=8Hz). lC-MS (m/z) = 164.2 ([M+H]+).

References

[1] Patent: WO2005/82901, 2005, A1. Location in patent: Page/Page column 33; 61
[2] Patent: WO2007/103755, 2007, A2. Location in patent: Page/Page column 51; 83