112029-98-8

General procedure for the synthesis of 1-methyl-4-(hydroxymethyl)pyrazole from 1-methyl-1H-pyrazole-4-carboxaldehyde: 1-methyl-1H-pyrazole-4-carboxaldehyde (3.48 g, 31.6 mmol) was dissolved in methanol (25 mL), and sodium borohydride (2.50 g, 66.1 mmol, 2.09 eq.) was added in batches under conditions of vigorous gas release. The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was then cooled to 0 °C and acidified by slow addition of aqueous 5N hydrochloric acid (20 mL) over 55 min to a pH of about 1. A thick white slurry was formed during the reaction and stirring was continued for 1 h at room temperature. Subsequently, the reaction mixture was alkalized by slow addition of saturated aqueous potassium carbonate solution (53.4 wt% K2CO3, 6.04 M; 10 mL). A clarified colorless solution (pH = 1.1) was obtained, which was diluted with additional saturated potassium carbonate solution (200 mL) and extracted with ethyl acetate (2 × 200 mL). The ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give 1-methyl-4-(hydroxymethyl)pyrazole as a light yellow oil (3.44 g, 97% yield).

[1] Patent: WO2008/153870, 2008, A1. Location in patent: Page/Page column 30
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 13, p. 3777 - 3787
[3] Russian Journal of General Chemistry, 2010, vol. 80, # 5, p. 1001 - 1003
[4] Patent: US2013/96144, 2013, A1. Location in patent: Paragraph 0174
[5] Patent: EP3239135, 2017, A1. Location in patent: Paragraph 0132; 0133