1,2-Dibromoethane → Tert-butyl 4-(4-fluorobenzyl)-4-hydroxypiperidine-1-carboxylate

HRID 240390Notes

Reaction equation

HRID 240390 reaction equation
[Mg].BrCCBr.[F:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11]Cl)=[CH:9][CH:8]=1.[O:15]=[C:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1>C1COCC1.O>[F:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11][C:16]2([OH:15])[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:20][CH2:21]2)=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 78391,2-DibromoethaneHCID 96024-Fluorobenzyl chlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5462224Magnesium

Product 1

HCID 23526831Tert-butyl 4-(4-fluorobenzyl)-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a suspension of magnesium (1.2 g) and 1,2-dibromoethane (0.11 mL) in THF (30 mL) was added a solution of 4-fluorobenzyl chloride (6.3 mL) in THF (10 mL) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 1 hr at the same temperature. The reaction mixture was cooled to −78° C., a solution of tert-butyl 4-oxopiperidine-1-carboxylate (5.0 g) in THF (10 mL) was added thereto, and the mixture was allowed to warm to room temperature, and stirred for 2 days. To the reaction mixture was added water at 0° C., and then saturated aqueous potassium sodium tartrate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and recrystallized from ethyl acetate/hexane to give the title compound (4.8 g).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 2 days
  3. extractionsaturated aqueous potassium sodium tartrate solution, and the mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)
  8. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-1985f382c63c47e48eec7d952b47fc60
Source dataset
uspto-grants-2014_02
Patent number
US08648079B2

Reaction notes

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