Water → (R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine

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Reaction Conditions

Reaction Steps

To a 5 L glass flask equipped with a mechanical stirrer and thermometer was charged with 584 g (315 g after corrected by wt %, 1.28 mol) of N-[1-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-acetamide and 1.2 L of purified water. The mixture was agitated at 60-65° C. for 3 h, forming a homogeneous solution. After cooling the batch to 40-45° C., 214 g (5.14 mol) of NaOH (solid) was added in portions. The mixture was agitated at 90° C. for 24 h. The mixture was cooled to 20-25° C. and extracted with 2 kg of isopropyl acetate. The combined organic phase was concentrated by distillation in vacuo (35-45° C. (batch)/P<−0.1 MPa) to give a yellow oil. The residue was diluted with 414 g of methyl tert-butyl ether and 750 g of heptane subsequently. The resulting suspension was stirred at 20-25° C. for 15 h. The solids were collected by filtration and washed with 1100 g of methyl tert-butyl ether/heptane (1/2, v/v). The solids were dried in a vacuum oven (30-35° C./P≦−0.1 MPa) for ca. 24 h to afford 215 g (68% yield in 2 steps) of 1-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine as an off-white solid. 1H-NMR (400 MHz, d6-DMSO): δ 7.31 (s, 1H), 5.38 (s, 1H), 4.55 (s, 2H), 4.26-4.32 (m, 1H), 3.92-3.98 (m, 3H), 3.7-3.73 (m, 1H), 1.31 (s, 3H), 1.25 (s, 3H).

Provenance & Evidence