Potassium Fluoride → methyl (2S)-3-[4-(3-amino-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanoate

Participants

Reaction Conditions

Reaction Steps

Butyl di-1-adamantylphosphine (1.07 g, 2.98 mmol), Pd(OAc)2 (0.33 mg, 1.49 mmol), dioxane (12 mL) and water (2.4 mL) were added to an oven-dried flask and stirred for 10 minutes. 3-bromo-5-methylaniline (1.58 g, 8.51 mmol), methyl (2S)-2-hydroxy-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanoate (3.5 g, 10.64 mmol), and potassium fluoride (1.24 g, 21.3 mmol) were added followed by additional dioxane (12 mL). The mixture was heated to 95° C. overnight then cooled to room temperature, filtered and diluted with water. The mixture was extracted with EtOAc (3×) and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0 to 80% EtOAc/hexanes) to afford methyl (2S)-3-[4-(3-amino-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanoate. MS ESI calcd. for C14H18N3O3 [M+H]+ 276. found 276. 1H NMR (500 MHz, DMSO-d6) δ 7.88 (s, 1H), 7.67 (s, 1H), 6.51 (s, 2H), 6.21 (s, 1H), 5.90 (d, J=6.1 Hz, 1H), 4.93 (s, 2H), 4.43 (tt, J=4.6 Hz, 9.2 Hz, 1H), 4.36 (d, J=4.2 Hz, 1H), 4.27-4.21 (m, 1H), 3.63 (s, 3H), 2.14 (s, 3H).

Provenance & Evidence