Methylamine → HCID 59761541, compound

A 40% methanolic solution (20.0 mL) of methylamine was added to a solution of ethyl 4-oxocyclohexanecarboxylate (10.0 g) in diethyl ether (100 mL) and stirred at room temperature for 5.5 hours. Drylite (10.0 g) was added thereto followed by stirring at room temperature for 18 hours. After it was filtered, the filtrate was concentrated. The resulting residue was dissolved in toluene (100 mL), then triethylamine (8.20 mL) and 2-iodobenzoyl chloride (10.97 g) were added thereto and the mixture was stirred for 2 days at 80° C. in a nitrogen atmosphere. A saturated sodium bicarbonate solution was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over sodium sulfate, filtered and concentrated in vacuo. It was purified by a silica gel column chromatography (hexane/ethyl acetate=9/1→3/1). The resulting residue was dissolved in acetonitrile (200 mL), then potassium carbonate (10.70 g), tetraethylammonium chloride (6.42 g), triphenylphosphine (2.03 g) and palladium acetate (869 mg) were added thereto and the mixture was stirred for 17 hours at 80° C. in a nitrogen atmosphere. Water was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over sodium sulfate, filtered and concentrated in vacuo. It was purified by a silica gel column chromatography (hexane/ethyl acetate=3/1→3/2). The resulting solid was suspended in diisopropyl ether and filtered to give the aimed compound (7.36 g, 44%) as a light yellow solid.

1. additionDrylite (10.0 g) was added
2. stirringby stirring at room temperature for 18 hours
3. filtrationAfter it was filtered
4. concentrationthe filtrate was concentrated
5. dissolutionThe resulting residue was dissolved in toluene (100 mL)
6. additiontriethylamine (8.20 mL) and 2-iodobenzoyl chloride (10.97 g) were added
7. stirringthe mixture was stirred for 2 days at 80° C. in a nitrogen atmosphere
8. additionA saturated sodium bicarbonate solution was added to the reaction solution
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with a saturated saline solution
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customIt was purified by a silica gel column chromatography (hexane/ethyl acetate=9/1→3/1)
15. dissolutionThe resulting residue was dissolved in acetonitrile (200 mL)
16. additionpotassium carbonate (10.70 g), tetraethylammonium chloride (6.42 g), triphenylphosphine (2.03 g) and palladium acetate (869 mg) were added
17. stirringthe mixture was stirred for 17 hours at 80° C. in a nitrogen atmosphere
18. additionWater was added to the reaction solution
19. extractionthe mixture was extracted with ethyl acetate
20. washThe organic layer was washed with a saturated saline solution
21. dry with materialdried over sodium sulfate
22. filtrationfiltered
23. concentrationconcentrated in vacuo
24. customIt was purified by a silica gel column chromatography (hexane/ethyl acetate=3/1→3/2)
25. filtrationfiltered

ORD record

ord-30c9cdfc6bb14cf5b7fd7bc45aefad7a

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960402B2