反应详情

温度

62.5 °C

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).

1. customTo a 5 L glass flask equipped with a mechanical stirrer
2. customforming a homogeneous solution
3. temperatureAfter cooling the batch to 40-45° C.
4. stirringThe mixture was agitated at 90° C. for 24 h
5. temperatureThe mixture was cooled to 20-25° C.
6. extractionextracted with 2 kg of isopropyl acetate
7. concentrationThe combined organic phase was concentrated by distillation in vacuo (35-45° C. (batch)/P<−0.1 MPa)
8. customto give a yellow oil
9. stirringThe resulting suspension was stirred at 20-25° C. for 15 h
10. filtrationThe solids were collected by filtration
11. washwashed with 1100 g of methyl tert-butyl ether/heptane (1/2
12. customThe solids were dried in a vacuum oven (30-35° C./P≦−0.1 MPa) for ca. 24 h