The general procedure for the synthesis of 5-methylthiazole-2-methanol from 2-methylthiazole-5-carbaldehyde was as follows:
1. a solution of n-BuLi (8.4 mL, 13.48 mmol) in THF (30 mL) was cooled to -70 °C under nitrogen protection and 2-bromo-5-methylthiazole (2.0 g, 11.23 mmol) was added slowly and dropwise.
2. Continue stirring the reaction mixture at -70 °C for 1.5 hours.
3. Maintaining -70 °C and nitrogen protection, DMF (1.3 mL, 16.85 mmol) was added dropwise to the reaction system and stirred at this temperature for 1 hour.
4. Quench the reaction with saturated aqueous ammonium chloride solution (5 mL) and partition the mixture between ethyl acetate and water.
5. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give a yellow oil.
6. The yellow oily substance was dissolved in methanol (15 mL) and sodium borohydride (512 mg, 13.48 mmol) was added in batches under nitrogen protection and at -60 °C. The mixture was stirred at -60 °C and the reaction was quenched with ethyl acetate and water.
7. After stirring the reaction mixture at -60 °C for 1 h, the reaction was quenched with acetone and concentrated.
8. The residue was partitioned between ethyl acetate and water, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated.
9. Purification by silica gel column chromatography using petroleum ether/ethyl acetate (3:1, v/v) as eluent gave 5-methylthiazole-2-methanol (1.3 g, 90.3% yield) as a brown oil.
LCMS retention time: 0.366 min; LCMS (MH+): 130.
