2-萘酚 → 3-(Naphthalen-2-yloxy)propan-1-amine

温度

80 °C

2-Naphthol (2.9 g, 20 mmol) in dry THF (40 ml) was treated with 60% NaH suspension (0.96 g) at room temperature. After hydrogen evolution ceased, 3-bromopropylphthalimide (5.36 g, 20 mmol) was added and the mixture was heated at 80° C. overnight. The reaction was cooled, diluted with ethyl acetate and water. The layers were separated and the aqueous layer extracted 3 times with ethyl acetate. The combined organic layers were then extracted 5 times with 5% aqueous potassium carbonate, dried over sodium sulfate and concentrated in vacuo. The crude product (observed as a single spot by TLC) was taken up in methanol (60 ml), treated with anhydrous hydrazine (4 ml) and refluxed for 3.5 hours. The mixture was cooled to 4° C. for several hours, then filtered. The filtrate was concentrated to dryness, then partitioned between dichloromethane and 2.5 M aqueous sodium hydroxide. The organic layer was washed with saturated sodium chloride solution, dried and concentrated in vacuo to give 3-(2-naphthyloxy)propyl amine as a beige solid, 1.14 g. The amine (1.14 g, 5.7 mmol) was treated with benzotriazole carboxamidinium 4-methylbenzenesulfonate (1.89 g, 5.7 mmol) and DIEA (1.39 ml) in a mixture of acetonitrile (8 ml) and DMF (2 ml) with shaking at room temperature overnight. Precipitation with ether gave amino(3-(2-naphthyloxy)propyl)carboxamidinium 4-methylbenzenesulfonate as a white crystalline solid. This guanidine (100 mg) was reacted (65 hours, 105° C.) with resin (100 mg) in accordance with the method described in Example 10 (i.e., Resin Method C) to give the title compound.

1. temperatureThe reaction was cooled
2. customThe layers were separated
3. extractionthe aqueous layer extracted 3 times with ethyl acetate
4. extractionThe combined organic layers were then extracted 5 times with 5% aqueous potassium carbonate
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated in vacuo
7. additiontreated with anhydrous hydrazine (4 ml)
8. temperaturerefluxed for 3.5 hours
9. temperatureThe mixture was cooled to 4° C. for several hours
10. filtrationfiltered
11. concentrationThe filtrate was concentrated to dryness
12. custompartitioned between dichloromethane and 2.5 M aqueous sodium hydroxide
13. washThe organic layer was washed with saturated sodium chloride solution
14. customdried
15. concentrationconcentrated in vacuo

ORD记录

ord-f520d471b7f146fab0c98c39d8b4da76

来源数据集

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

专利号

US07425557B2