Benzyl Bromide → HCID 18374750, compound

HRID 2301183Notes

Reaction equation

HRID 2301183 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][OH:17])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:18]([O:17][CH2:16][CH:13]1[CH2:14][CH2:15][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])[CH2:11][CH2:12]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydride2×HCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 18374750HCID 18374750, compoundYield 165.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (60% oil dispersion, 53 mg, 1.3 mmol) was added in portions to a solution of 1-(tert-butoxycarbonyl)-4-(hydroxymethyl)piperidine (240 mg, 1.1 mmol) and benzyl bromide (0.40 mL, 0.58 g, 0.33 mmol) in DMF (2.0 mL). After 1 h, additional NaH (60% oil disperison, 15 mg, 0.38 mmol) was added. After a total of 2.25 h, the mixture was quenched with water and extracted with EtOAc. The organic layer was washed with saturated aq. NaCl, dried (Na2SO4), and evaporated. Purification by flash column chromatogaraphy on silica gel, eluting with 5-10% EtOAc in hexane gave 167 mg of 4-(benzyloxymethyl)-1-(tert-butoxycarbonyl)piperidine. A portion (160 mg, 0.55 mmol) of this intermediate was dissolved in CH3OH (2.0 mL) and a solution of HCl (2 N in ether, 2.0 mL, 4 mmol) was added. The mixture was stirred overnight at RT and evaported to give the title compound as a white solid.

Workup

  1. customAfter a total of 2.25 h, the mixture was quenched with water
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with saturated aq. NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customPurification by flash column chromatogaraphy on silica gel
  7. washeluting with 5-10% EtOAc in hexane

Sources & evidence

ORD record
ord-02d9f636776a495eb4eca805ec6b7b7c
Source dataset
uspto-grants-2002_12
Patent number
US06498161B1

Reaction notes

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