4-Methylmorpholine → 4-Chloro-2-methyl-N-(tetrahydro-pyran-4-yl)-benzamide

4-Chloro-2-methylbenzoic acid (2.06 g, 12 mmol) was dissolved in DCM (50 mL) and DMF (10 mL) and the solution was cooled to an ice-water bath. To this solution was added a solution of tetrahydropyran-4-yl amine (1.22 g, 12 mmol, 1.05 equiv.) in 10 mL of DCM, followed by N-methylmorpholine (5.75 g, 8 mL, 75 mmol, 3 equiv.), 1-hydroxylbenzotriazole (HOBT) (4.4 g, 32.5 mmol, 1.3 equiv.), sequentially, and finally EDC.HCl (2.97 g, 15.6 mmol, 1.3 equiv.). The resultant clear light brown solution was stirred at r.t. overnight. TLC (5% MeOH in DCM) and LC/MS detected the product peak at retention time of 2.878 min with MS 284/286. The reaction was quenched with saturated sodium bicarbonate aqueous solution (10 mL) and 10 mL of DCM. The two layers were separated, and the aqueous layer was extracted with DCM (15 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (10 mL), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuo to get 2.09 g (69% yield) of the titled compounds as white solid.

1. customThe reaction was quenched with saturated sodium bicarbonate aqueous solution (10 mL) and 10 mL of DCM
2. customThe two layers were separated
3. extractionthe aqueous layer was extracted with DCM (15 mL×2)
4. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (10 mL)
5. dry with materialdried (anhydrous potassium carbonate)
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORDレコード

ord-26db395bbf32461089582004dba602c9

出典データセット

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08871788B2