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

HRID 717269Notes

Reaction equation

HRID 717269 reaction equation
[Mg].BrCCBr.[Br:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11]Br)=[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.[Cl-].[NH4+]>C(OCC)C>[Br: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 5

HCID 78391,2-DibromoethaneHCID 25517Ammonium ChlorideHCID 685274-Bromobenzyl bromideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5462224Magnesium

Product 1

HCID 70851437Tert-butyl 4-(4-bromobenzyl)-4-hydroxypiperidine-1-carboxylateYield 40.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

To a suspension of magnesium (2.9 g) in diethyl ether (50 mL) was added dropwise 1,2-dibromoethane (0.90 mL) at room temperature, and the reaction mixture was vigorously stirred at room temperature for 20 min. To the reaction mixture was added dropwise a solution of 4-bromobenzyl bromide (25 g) in diethyl ether (150 mL) over 30 min or more at 0° C., and then added dropwise a solution of tert-butyl 4-oxopiperidine-1-carboxylate (16 g) in diethyl ether (200 mL) over 30 min or more 0° C. The reaction mixture was allowed to warm to room temperature, and stirred at room temperature for 3 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution (200 mL), and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (12 g).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred at room temperature for 3 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4e7be2144c61472e847794a42294ea22
Source dataset
uspto-grants-2015_11
Patent number
US09193709B2

Reaction notes

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