Tetrahydrofuran → 4-(4-Fluorophenyl)-3-formylpiperidine-6-one

Temperature

-70 °C

DIBAL-H (4.03 ml, 6 mmol) was added gradually at a rate of 5.6 ml/hour, by means of a syringe pump, to a solution of 3-carboxyethyl-4-(4-fluorophenyl)-piperidine-6-one (0.53 g, 2 mmol) in 4 ml tetrahydrofuran at −70° C. under an argon atmosphere. The reaction mixture was stirred for 1 hour at −70° C. then quenched with a solution of methanol (0.24 ml) in toluene (2 ml) at −70° C., followed by 0.12 ml water at 0° C. After 30 minutes stirring at ambient temperature, the gel which formed was destroyed by the addition of 1.5 ml brine and the reaction mixture was extracted with diethyl ether (50 ml). The organic phase was separated, dried with anhydrous sodium sulphate, filtered and evaporated to yield the title compound (0.2 g) as a yellow oil. The aqueous layer was basified with 10% aqueous sodium hydroxide and extracted with dichloromethane (20 ml). A further 0.08 g product was isolated from the dichloromethane extract.

1. customat −70° C.
2. customthen quenched with a solution of methanol (0.24 ml) in toluene (2 ml) at −70° C.
3. customfollowed by 0.12 ml water at 0° C
4. stirringAfter 30 minutes stirring at ambient temperature
5. customthe gel which formed
6. customwas destroyed by the addition of 1.5 ml brine
7. extractionthe reaction mixture was extracted with diethyl ether (50 ml)
8. customThe organic phase was separated
9. dry with materialdried with anhydrous sodium sulphate
10. filtrationfiltered
11. customevaporated

ORD record

ord-686be3697c9340988bd955052b8b0dc7

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06489347B1