Diethyl Ether → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 384701Notes

Reaction equation

[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1([C:21](OCC)=[O:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.CCOCC>C1COCC1.C(Cl)(Cl)Cl>[F:7][C:8]1([CH2:21][OH:22])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 0 °C

Procedure

Lithium aluminium hydride (1M in THF) (2.36 mL, 2.361 mmol) was added dropwise to a stirred solution of 1-tert-butyl 4-ethyl 4-fluoropiperidine-1,4-dicarboxylate (325 mg, 1.180 mmol) in THF (5.90 mL) cooled to 0° C. After 10 min ether (15 mL) was added and the reaction was quenched by sequential dropwise addition of water (0.1 mL), 10% NaOH (0.1 mL) and water (0.3 mL). The mixture was stirred at room temperature and the lithium salts that had precipitated were filtered off and washed with fresh ether. The organic filtrates were combined and solvent was removed in vacuo to leave a clear gum. The crude product was taken up in chloroform and loaded onto a 25+M Biotage silica column. Chromatography, eluting with a gradient of EtOAc in hexanes, gave tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (189 mg, 0.810 mmol, 69%) as a clear gum.

Workup

customthe reaction was quenched by sequential dropwise addition of water (0.1 mL), 10% NaOH (0.1 mL) and water (0.3 mL)
customthe lithium salts that had precipitated
filtrationwere filtered off
washwashed with fresh ether
customsolvent was removed in vacuo
customto leave a clear gum
washChromatography, eluting with a gradient of EtOAc in hexanes

Sources & evidence

ORD record: ord-6e1add202b5145a99aee42489b98cbe3
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367658B2

Reaction notes

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