Reaktion #534965

Reaktionsgleichung

sodium triacetoxyborohydride

sodium triacetoxyborohydride

triethylamine

tetrahydro-4H-pyran-4-one

triethylamine

tetrahydro-4H-pyran-4-one

4-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

→

4-fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Lösungsmittel

1,2-dichloroethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred at room temperature for one overnight
2. 2
   SonstigeReaction mixture
3. 3
   Sonstigewas quenched with NaHCO3 (saturated solution)
4. 4
   workup.ADDITIONdiluted with dichloromethane
5. 5
   Sonstigethe two phases were separated
6. 6
   Sonstigethe organic solvent was evaporated
7. 7
   Sonstigeto afford the crude product
8. 8
   SonstigeThe crude obtained
9. 9
   workup.STIRRINGthe mixture was stirred at room temperature for 10 minutes
10. 10
    workup.STIRRINGthe mixture was stirred at room temperature for 3 extra hours
11. 11
    SonstigeReaction mixture
12. 12
    Sonstigewas quenched with NaHCO3 (saturated solution)
13. 13
    workup.ADDITIONdiluted with dichloromethane
14. 14
    Sonstigethe two phases were separated
15. 15
    Sonstigethe organic solvent was evaporated
16. 16
    Sonstigeto afford the crude product that
17. 17
    Sonstigewas purified by chromatography (methanol-NH3-dichloromethane)

Vorschrift

4-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D5) (0.072 mmol, 21 mg) was dissolved in dichloromethane (2 ml) and triethylamine (3 eq., 0.216 mmol, 30 microliters), tetrahydro-4H-pyran-4-one (7 eq., 0.5 mmol, 47 microliters) were added and the mixture was stirred at room temperature for 10 minutes; sodium triacetoxyborohydride (7 eq., 0.5 mmol, 106 mg) was added at room temperature and the mixture was stirred at room temperature for one overnight. Reaction mixture was quenched with NaHCO3 (saturated solution) and diluted with dichloromethane; the two phases were separated and the organic solvent was evaporated to afford the crude product. The crude obtained was dissolved in 1,2-dichloroethane (3 ml) and triethylamine (3 eq., 0.216 mmol, 30 microliters), tetrahydro-4H-pyran-4-one (7 eq., 0.5 mmol, 47 microliters) were added again and the mixture was stirred at room temperature for 10 minutes; sodium triacetoxyborohydride (7 eq., 0.5 mmol, 106 mg) was subsequently added at room temperature and the mixture was stirred at room temperature for 3 extra hours. Reaction mixture was quenched with NaHCO3 (saturated solution) and diluted with dichloromethane; the two phases were separated and the organic solvent was evaporated to afford the crude product that was purified by chromatography (methanol-NH3-dichloromethane) to afford 4-fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 10 mg, 42%, M++H=334, which was converted to the HCl salt using 1M HCl in diethyl ether.

Quelle