Triethylamine → 2-(3-Chlorophenyl)-4,5-dihydro-4-[(4-methylphenyl)methyl]oxazole

A solution of 1.75 g (10 millimoles) of 3-chlorobenzoyl chloride in 15 ml of tetrahydrofuran was added with ice cooling and stirring to a 100 ml egg-plant-shaped flask containing 1.61 g (10 millimoles) of 2-amino-3-(4-methyl-phenyl)-1-propanol, 1.01 g (10 millimoles) of triethylamine and 30 ml of tetrahydrofuran over the course of 30 minutes. The mixture was further stirred at 20° C. for 3 hours. The resulting triethylamine hydrochloride was removed by a glass filter, and the filtrate was concentrated under reduced pressure. Thionyl chloride (5 ml; 68 millimoles) was added all at once to a 100 ml eggplant-shaped flask containing this concentrate and 30 ml of benzene. With stirring, the mixture was refluxed for 3 hours. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The concentrate was dissolved in 100 ml of ethyl acetate, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. A 100 ml eggplant-shaped flask containing this concentrate and 30 ml of ethanol was heated to 70° C. over an oil bath with stirring, and 15 ml of a 3 % aqueous solution of sodium hydroxide was added over 10 minutes. The mixture was further stirred at 70° C. for 20 minutes, and concentrated under reduced pressure. Benzene (100 ml) was added to the concentrate, and the mixture was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=7/3) to give 2-(3-chlorophenyl)-4-(4-methylbenzyl) -2-oxazoline (compound No. 108) as a yellow viscous oil. Yield 1.7 g (59.5 %).

1. stirringThe mixture was further stirred at 20° C. for 3 hours
2. customThe resulting triethylamine hydrochloride was removed by a glass
3. filtrationfilter
4. concentrationthe filtrate was concentrated under reduced pressure
5. additioncontaining
6. concentrationthis concentrate
7. stirringWith stirring
8. temperaturethe mixture was refluxed for 3 hours
9. concentrationconcentrated under reduced pressure
10. dissolutionThe concentrate was dissolved in 100 ml of ethyl acetate
11. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated under reduced pressure
14. additionA 100 ml eggplant-shaped flask containing
15. concentrationthis concentrate
16. temperature30 ml of ethanol was heated to 70° C. over an oil bath
17. stirringwith stirring
18. addition15 ml of a 3 % aqueous solution of sodium hydroxide was added over 10 minutes
19. stirringThe mixture was further stirred at 70° C. for 20 minutes
20. concentrationconcentrated under reduced pressure
21. additionBenzene (100 ml) was added to the concentrate
22. washthe mixture was washed with a saturated aqueous solution of sodium chloride
23. dry with materialdried over anhydrous sodium sulfate
24. concentrationconcentrated under reduced pressure
25. customThe concentrate was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=7/3)

ORD record

ord-3ec81aaa9eec4227bd424a99949c6940

Source dataset

uspto-grants-1990_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04977171