Triethylamine → HCID 57934506, compound

To a solution of 3-(3,5-dimethoxyphenyl)propan-1-ol (24.3 g) in ethyl acetate (500 ml) were sequentially added triethylamine (16.3 g) and methanesulfonyl chloride (16.3 g) on an ice bath, and the solution was stirred for 25 minutes at room temperature. The solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. To a solution of the total amount of the resulting 3-(3,5-dimethoxyphenyl)propyl methanesulfonate (crude product) in N,N-dimethylformamide (150 ml) was added sodium cyanide (15.2 g), and the solution was stirred for 8.5 hours at 80° C. The solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. To a solution of the total amount of the resulting 4-(3,5-dimethoxyphenyl)butyronitrile (crude product) in ethylene glycol (100 ml) was added an aqueous solution of 5N sodium hydroxide (75 ml), and the solution was refluxed for 9.5 hours. The reaction solution was acidified with concentrated sulfuric acid, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. To a solution of the resulting residue in ethanol (400 ml) was added concentrated sulfuric acid (4 ml), and the solution was stirred for 1 hour and 20 minutes at 70° C. The reaction solution was concentrated in vacuo, extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (25.3 g).

1. extractionThe solution was extracted with ethyl acetate
2. washsequentially washed with water and brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customthe solvent was evaporated in vacuo
5. additionTo a solution of the total amount of the resulting 3-(3,5-dimethoxyphenyl)propyl methanesulfonate (crude product) in N,N-dimethylformamide (150 ml) was added sodium cyanide (15.2 g)
6. stirringthe solution was stirred for 8.5 hours at 80° C
7. extractionThe solution was extracted with ethyl acetate
8. washsequentially washed with water and brine
9. dry with materialdried over anhydrous magnesium sulfate
10. customthe solvent was evaporated in vacuo
11. additionTo a solution of the total amount of the resulting 4-(3,5-dimethoxyphenyl)butyronitrile (crude product) in ethylene glycol (100 ml) was added an aqueous solution of 5N sodium hydroxide (75 ml)
12. temperaturethe solution was refluxed for 9.5 hours
13. extractionthe solution was extracted with ethyl acetate
14. washsequentially washed with water and brine
15. dry with materialdried over anhydrous magnesium sulfate
16. customthe solvent was evaporated in vacuo
17. additionTo a solution of the resulting residue in ethanol (400 ml) was added concentrated sulfuric acid (4 ml)
18. stirringthe solution was stirred for 1 hour and 20 minutes at 70° C
19. concentrationThe reaction solution was concentrated in vacuo
20. extractionextracted with ethyl acetate
21. washsequentially washed with water and brine
22. dry with materialdried over anhydrous magnesium sulfate
23. customthe solvent was evaporated in vacuo
24. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate system)

ORD record

ord-084c1443d22a4ae7bd5ddf65b8ae44b9

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07612114B2