Hydrochloric Acid → HCID 86668254, compound

Tert-butyl 4-(cyclopropylmethyl)piperazine-1-carboxylate 31a (2 g, 8.30 mmol) was dissolved in 40 mL of dichloromethane followed by the addition of 20 mL of a 4 M solution of hydrogen chloride in dioxane. The reaction solution was stirred for 0.5 hours. The reaction solution was concentrated under reduced pressure followed by the addition of 40 mL of dichloromethane and dropwise with 20 mL of triethylamine to adjust pH to 10 to 11. The resulting solution was concentrated under reduced pressure. The residue was added with 50 mL of ethyl acetate and filtered. The filtrate was concentrated under reduced pressure, added with 50 mL of ethyl acetate and 20 mL of water, then added with (R)-2-chloromethyl-oxirane (0.92 g, 9.96 mmol) and sodium hydroxide (0.66 g, 16.60 mmol). The reaction solution was stirred for 12 hours. The reaction solution was concentrated under reduced pressure, added with 50 mL of water and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL), dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 1-(cyclopropylmethyl)-4-[[(2R)-oxiran-2-yl]methyl]piperazine 31b (0.91 g, yield: 57.0%) as a yellow oil.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. additionfollowed by the addition of 40 mL of dichloromethane and dropwise with 20 mL of triethylamine
3. concentrationThe resulting solution was concentrated under reduced pressure
4. additionThe residue was added with 50 mL of ethyl acetate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under reduced pressure
7. additionadded with 50 mL of ethyl acetate and 20 mL of water
8. stirringThe reaction solution was stirred for 12 hours
9. concentrationThe reaction solution was concentrated under reduced pressure
10. additionadded with 50 mL of water
11. extractionextracted with dichloromethane (50 mL×3)
12. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL)
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationThe filtrate was concentrated under reduced pressure
15. customThe resulting residue was purified by silica gel column chromatography

ORD record

ord-36cd7a9aa6e544cb8e6c432859f019d3

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691822B2