Hydrochloric Acid → Methyl (S)-2-amino-3-cycloheptylpropanoate

Temperature

-50 °C

At −78° C. 7.80 ml (19.5 mmol) n-butyllithium (2.5 M in hexane) were added dropwise to 2.90 ml (16.2 mmol) (R)-2-isopropyl-3.6-dimethoxy-2,5-dihydropyrazine in 55 ml THF and the mixture was stirred for 2 h at −50° C. Then at −70° C. 4.25 g (17.8 mmol) (iodomethyl)cycloheptane in 15 ml THF were added dropwise, then the mixture was stirred for 30 min at −78° C., for 3 h at 0° C. and overnight at RT. After the addition of water and methanol it was stirred for 20 min at RT. Ethyl acetate was added and the mixture was extracted with saturated, aqueous saline solution. The organic phase was dried and evaporated to dryness by rotary evaporation. The residue was purified by flash chromatography. The fractions containing the product were combined and concentrated by rotary evaporation. The residue obtained was combined with acetonitrile, water and 1M hydrochloric acid and stirred overnight at RT. The acetonitrile was evaporated off and the aqueous phase was neutralised with potassium hydrogen carbonate. It was extracted with ethyl acetate. The combined organic phases were dried and evaporated to dryness by rotary evaporation.

1. customAt −78° C
2. customat −70° C
3. stirringthe mixture was stirred for 30 min at −78° C., for 3 h at 0° C. and overnight at RT
4. stirringwas stirred for 20 min at RT
5. extractionthe mixture was extracted with saturated, aqueous saline solution
6. customThe organic phase was dried
7. customevaporated to dryness by rotary evaporation
8. customThe residue was purified by flash chromatography
9. additionThe fractions containing the product
10. concentrationconcentrated by rotary evaporation
11. customThe residue obtained
12. stirringstirred overnight at RT
13. customThe acetonitrile was evaporated off
14. extractionIt was extracted with ethyl acetate
15. customThe combined organic phases were dried
16. customevaporated to dryness by rotary evaporation

ORD record

ord-14a76f18eb9c435499306f2afcd4ae84

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765763B2