Sodium borohydride → N-{4-[(1R)-1-aminopropyl]-2-ethylphenyl}methanesulfonamide

Temperature

80 °C

To a stirred solution of N-(2-ethyl-4-propionylphenyl)methanesulfonamide (7.8 mmol) in tetrahydrofuran (15 ml) and titanium (IV) ethoxide (15 ml), (R)-(+)-2-methyl-2-propanesulfinamide (7.8 mmol) was added. The mixure was stirred at 80° C. for 16 hours. Upon completion, as determined by LC-MS, the mixture was cooled to room temperature and then to 0° C. before it was added dropwise into a 0° C. solution of sodium borohydride (1.18 g, 31 mmol) in tetrahydrofuran (15 ml). The mixture was stirred at 0° C. for 3 hours and then quenched with methanol. After stirring at room temperature for 2 hours, Celite pad and water were added to the mixture, filtered thorough Celite, and washed with dichloromethane-ethyl acetate-methanol. The filtration was evaporated under the reduced pressure and the given residue was purified by silica gel eluting with dichloromethane-ethyl acetate (1:1) to afford the title compound as yellow oil. It was dissolved in methanol (30 ml) and hydrogen chloride-methanol (30 ml) was added. The solution was stirred at room temperature for 1 hour. After the solvent was removed under the reduced pressure, the product was recrystalized from diethylether-methanol to afford the desired product as hydrogen chloride salt.

1. temperaturethe mixture was cooled to room temperature
2. stirringThe mixture was stirred at 0° C. for 3 hours
3. customquenched with methanol
4. stirringAfter stirring at room temperature for 2 hours
5. additionCelite pad and water were added to the mixture
6. filtrationfiltered thorough Celite
7. washwashed with dichloromethane-ethyl acetate-methanol
8. filtrationThe filtration
9. customwas evaporated under the reduced pressure
10. customthe given residue was purified by silica gel eluting with dichloromethane-ethyl acetate (1:1)

ORD record

ord-e8cd7b4ff2234f28ad84ba001235310c

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622589B2