反应详情

温度

80 °C

On a larger scale, ethyl 6-bromo-4-chloroquinoline-3-carboxylate (2196 g, (1976 g active), 6.28 mol) was charged to the vessel with DMA (16 L). Tetrahydro-2H-pyran-4-amine (1224 g, 12.10 mol) was added over 10 minutes with an observed exotherm of 21-27° C. DIPEA (3.5 L, 20.09 mol) was added with no observed exotherm. The mixture was heated to 75-85° C. and the resulting solution stirred for 18.5 h at 80° C. HPLC indicated consumption of starting material and 99.2% product. The reaction was cooled to 50° C. and then poured into water (50 L). The resulting suspension was stirred for 2 h at r.t. and the solids isolated by filtration, washing with water (8 L then 2×4 L). The solid was dried under vacuum at 40° C. for 55 h to give 2307 g of desired material. Analytical data was consistent with that obtained from previous batches.

1. customconsumption of starting material and 99.2% product
2. temperatureThe reaction was cooled to 50° C.
3. additionpoured into water (50 L)
4. stirringThe resulting suspension was stirred for 2 h at r.t.
5. customthe solids isolated by filtration
6. washwashing with water (8 L
7. customThe solid was dried under vacuum at 40° C. for 55 h