Diisobutylaluminum hydride → Benzyl 4-formylpiperidine-1-carboxylate

Temperature

-60 °C

To a solution of 1-benzyloxycarbonyl-piperidine-4-carboxylic acid methyl ester (2.0 g, 7.2 mmol) in anhydrous toluene (20 mL) at −78° C. was added DIBAL-H (15.2 mL of a 1 M solution in hexane, 15.2 mmol, 2 eq.) in a drop-wise fashion. The mixture was stirred at −60° C. for 2 h then quenched by addition of 1 N HCl. The resulting mixture was extracted with EtOAc (3×50 mL) and the combined organic extracts were washed with saturated brine (50 mL) then dried over Na2SO4, filtered and concentrated by rotary evaporation. The crude residue was purified by flash column chromatography by eluting 9:1 toluene/EtOAc to give 1-benzyloxycarbonyl-piperidine-4-carboxaldehyde as a colorless gum (0.49 g, 2.09 mmol, 28%). 1H NMR (300 MHz, CDCl3): δ9.75 (s, 1H), 7.46 (m, 5H), 5.24 (s, 2H), 4.15 (m, 2H), 3.12 (t, 2H), 2.54 (m, 1H), 2.02 (m, 2H), 1.68 (m, 2H).

1. customthen quenched by addition of 1 N HCl
2. extractionThe resulting mixture was extracted with EtOAc (3×50 mL)
3. washthe combined organic extracts were washed with saturated brine (50 mL)
4. dry with materialthen dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated by rotary evaporation
7. customThe crude residue was purified by flash column chromatography
8. washby eluting 9:1 toluene/EtOAc

ORD record

ord-a239f13bb9e84b27a7e6a9685843e7bd

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06887889B2