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

HRID 1095716Notes

Reaction equation

HRID 1095716 reaction equation
CC[O:3][C:4]([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)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:19][C:6]1([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

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 89.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-Fluoro-1-(1,1-dimethylethyl)1,4-piperidinedicarboxylic acid-4-ethyl ester (0.40 g, 1.45 mmol) was dissolved in THF (1.5 mL), cooled to 0° C. and treated with lithium aluminum hydride (1 M in THF, 2.90 ml, 2.90 mmol). The reaction mixture was stirred at 0° C. for 2 hours, then warmed to ambient temperature for 3 hours. The reaction was quenched with sequential additions of water (110 μL), 15% NaOH (110 μL), and water (330 μL), and then stirred for 20 minutes. The slurry was diluted with ethyl acetate and filtered. The filtrate was concentrated in vacuo to provide the desired product (0.303 g).

Workup

  1. temperaturewarmed to ambient temperature for 3 hours
  2. customThe reaction was quenched with sequential additions of water (110 μL), 15% NaOH (110 μL), and water (330 μL)
  3. stirringstirred for 20 minutes
  4. additionThe slurry was diluted with ethyl acetate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-ada7f32bcf474b1f93bee5db4ab5475d
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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