Oxygen → N-(2-hydroxymethylbutyl)-4-benzylpiperidine

A solution of diethylmagnesium (5 ml of a 0.8 M solution in diethyl ether, 4 mmol) was placed in a Schlenk tube and the solvent removed. The residue was dissolved in THF (1 ml). (Cyclopentadienyl)(1-[(1'S,2'S,5'R)-2'-isopropyl-5'-methylcyclohexyl]-4,5,6,7-tetrahydroindenyl)zirconium dichloride (prepared as in Example 1, 24 mg, 0.05 mmol) was added under positive argon flow followed by N-allyl-4-benzylpiperidine (0.215 g, 1 mmol) in THF (1 ml). The reaction mixture was stirred at room temperature overnight. The mixture was cooled to 0° C. and a balloon of oxygen gas added. The tube was flushed through with a small amount of oxygen and the reaction mixture was stirred overnight. The reaction mixture was poured into aqueous ammonium chloride solution (100 ml) and the aqueous was extracted with diethyl ether (3×50 ml). The organic extracts were combined, dried and evaporated to leave a residue which was purified by column chromatography (eluant 20% diethyl ether in petroleum ether) followed by Kugelrohr distillation (170° C., 1.0 mbar) to give the title compound as a clear oil which crystallised on standing (0.096 g, 37%, 42% ee).

1. customthe solvent removed
2. dissolutionThe residue was dissolved in THF (1 ml)
3. temperatureThe mixture was cooled to 0° C.
4. customThe tube was flushed through with a small amount of oxygen
5. stirringthe reaction mixture was stirred overnight
6. additionThe reaction mixture was poured into aqueous ammonium chloride solution (100 ml)
7. extractionthe aqueous was extracted with diethyl ether (3×50 ml)
8. customdried
9. customevaporated
10. customto leave a residue which
11. customwas purified by column chromatography (eluant 20% diethyl ether in petroleum ether)
12. distillationfollowed by Kugelrohr distillation (170° C., 1.0 mbar)

ORD record

ord-9ad60c0f06e14caaa992b68d44dadf77

Source dataset

uspto-grants-1999_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05929266