Aluminium lithium hydride → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 876449Notes

Reaction equation

HRID 876449 reaction equation
[F:1][C:2]1([C:15](OCC)=[O:16])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:1][C:2]1([CH2:15][OH:16])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 21306965Ethyl N-Boc-4-fluoropiperidine-4-carboxylate

Product 1

HCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylateYield 105.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 1-tert-butyl 4-ethyl 4-fluoropiperidine-1,4-dicarboxylate (3.0 g, 10.90 mmol) in 55 mL THF was added 1M lithium aluminum hydride in THF (21.79 mL, 21.79 mmol). The reaction mixture was stirred at 0° C. for 3.5 hours, after which it was carefully quenched by the addition of 1:1 Na2SO4-10H2O:Celite, diluted with THF, warmed to ambient temperature, and stirred vigorously for 2 hours. The slurry was vacuum filtered through GF/F paper on a Buchner funnel, rinsed with THF, and the filtrate was concentrated in vacuo to give the title compound (2.69 g) as a clear colorless oil, which was used without further purification.

Workup

  1. customafter which it was carefully quenched by the addition of 1:1 Na2SO4-10H2O
  2. additionCelite, diluted with THF
  3. temperaturewarmed to ambient temperature
  4. stirringstirred vigorously for 2 hours
  5. filtrationfiltered through GF/F paper on a Buchner funnel
  6. washrinsed with THF
  7. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-0a5e1c7be3ed4020aba82f8b5f48384a
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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