Diisobutylaluminumhydride → Tert-butyl 4-fluoro-4-(2-hydroxyethyl)piperidine-1-carboxylate

HRID 912532Notes

Reaction equation

C([O:3][C:4](=O)[CH2:5][C:6]1([F:19])[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)C.[H-].C([Al+]CC(C)C)C(C)C>C(Cl)Cl>[F:19][C:6]1([CH2:5][CH2:4][OH:3])[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:10][CH2:11]1

Participants

Conditions

Temperature: -78 °C

Procedure

To tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-fluoropiperidine-1-carboxylate (3.8 g) in DCM (20 ml) at −78° C. under nitrogen was added by syringe diisobutylaluminum hydride (2.2M in Toluene, 24 ml). The mixture was stirred at −78° C. for 2 hours, then warmed up to room temperature. The mixture was then poured to ice (100 g), acidified to pH 3, and extracted with ethyl acetate (200 ml+100 ml×3). Combined ethyl acetate layer was then dried over sodium sulphate, solvent removed to give tert-butyl 4-fluoro-4-(2-hydroxyethyl)piperidine-1-carboxylate which is contaminated with HF eliminated allylic alcohol in ˜3:1 ratio in favour of desired product (3 g). As purification proved to be difficult, this was used for next step as a mixture.

Workup

temperaturewarmed up to room temperature
extractionextracted with ethyl acetate (200 ml+100 ml×3)
dry with materialCombined ethyl acetate layer was then dried over sodium sulphate, solvent
customremoved

Sources & evidence

ORD record: ord-4070304d461c4de9be23f34701797d17
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026236B2

Reaction notes

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