Potassium Hydroxide → 2-(4-Benzyloxy-2-methoxymethoxyphenyl)ethylamine

Temperature

65 °C

To a solution of 28.42 g of 3-(4-benzyloxy-2-methoxymethoxyphenyl)propionamide and 40.4 mL of 1,8-diazabicyclo[5.4.0]-7-undecene in 895 mL of methanol was added 16.04 g of N-bromosuccinimide at 65° C. After the mixture was stirred at 65° C. for 15 minutes, to the reaction mixture was added additional 16.04 g of N-bromosuccinimide at 65° C. After being stirred at 65° C. for 15 minutes, the resulted mixture was concentrated under reduced pressure to remove the solvent. To the residue were added water and ethyl acetate, and the organic layer was separated. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give oily product. To a solution of this residue in 242 mL of ethanol was added 67.6 mL of 8 mol/L aqueous potassium hydroxide solution, and the mixture was refluxed for 15 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. To the residue were added 500 mL of ethyl acetate, 50 mL of toluene, and 300 mL of water, and the organic layer was separated. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by medium pressure liquid column chromatography on silica gel (eluent: hexaneethyl acetate) to give 80.0 g of 2-(4-benzyloxy-2-methoxymethoxyphenyl)ethylamine as a colorless oil.

1. stirringAfter being stirred at 65° C. for 15 minutes
2. concentrationthe resulted mixture was concentrated under reduced pressure
3. customto remove the solvent
4. additionTo the residue were added water and ethyl acetate
5. customthe organic layer was separated
6. washThe organic layer was washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated under reduced pressure
10. customto give oily product
11. temperaturethe mixture was refluxed for 15 hours
12. concentrationThe reaction mixture was concentrated under reduced pressure
13. customto remove the solvent
14. additionTo the residue were added 500 mL of ethyl acetate, 50 mL of toluene, and 300 mL of water
15. customthe organic layer was separated
16. washThe organic layer was washed with water
17. dry with materialdried over anhydrous magnesium sulfate
18. filtrationfiltered
19. concentrationThe filtrate was concentrated under reduced pressure
20. customthe residue was purified by medium pressure liquid column chromatography on silica gel (eluent: hexaneethyl acetate)

ORD record

ord-e7cb90f08e8a456eb5d764c90bbfd996

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07563822B2