Lithium borohydride → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 401954Notes

Reaction equation

HRID 401954 reaction equation
C([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)C.[Li+].[BH4-]>C1COCC1>[C:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][C:6]([F:19])([CH2:4][OH:3])[CH2:11][CH2:10]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 21306965Ethyl N-Boc-4-fluoropiperidine-4-carboxylate

Product 1

HCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylateYield 86.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-fluoro-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (0.9 mmol, 0.25 g), in anhydrous THF (3 mL) under N2 atmosphere, was added LiBH4 (2.0 mmol, 1.0 mL, 2N solution in THF) dropwise and reaction was stirred at room temperature for 10 h. The reaction was quenched with slow addition of water (1 mL) and the product was extracted with ethyl acetate (2×5 mL), Organic layer was washed with water, (5 mL), brine (5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a SiO2 cartridge with 30% ethyl acetate in hexanes to provide 4-fluoro-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (0.182 g).

Workup

  1. customreaction
  2. customThe reaction was quenched with slow addition of water (1 mL)
  3. extractionthe product was extracted with ethyl acetate (2×5 mL), Organic layer
  4. washwas washed with water, (5 mL), brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on a SiO2 cartridge with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-12aeb3cda24d4e938b12bb9ccbb48570
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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