Benzyl Bromide → tert-butyl (3R,4R)-4-(4-benzyloxyphenyl)-3-hydroxy-piperidine-1-carboxylate

HRID 1507217Notes

Reaction equation

HRID 1507217 reaction equation
[OH:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C=O)C>[CH2:28]([O:14][C:11]1[CH:10]=[CH:9][C:8]([C@H:7]2[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3][C@@H:2]2[OH:1])=[CH:13][CH:12]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 11483231(3R,4R)-tert-Butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 52910991tert-butyl (3R,4R)-4-(4-benzyloxyphenyl)-3-hydroxy-piperidine-1-carboxylateYield 93.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (3R,4R)-tert-butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate (620 mg, 2.1 mmol, E-2 from step E), potassium carbonate (584 mg, 4.2 mmol), and benzyl bromide (0.25 mL, 2.1 mmol) in DMF (5 mL) was stirred at rt for 16 h. The solvent was removed by evaporation and the residue was treated with 50 mL of water. The aqueous mixture was then extracted 4 times with 50 mL of chloroform. The combined organic phases were dried over anhydous Na2SO4, filtered, and evaporated to yield 750 mg of (3R,4R)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-hydroxypiperidine-1-carboxylate which was used without further purification. LCMS (method F) RT 2.28 min, m/z=310 (M+H+−t-butyl −water), 328 (M+H+−t-butyl).

Workup

  1. customThe solvent was removed by evaporation
  2. additionthe residue was treated with 50 mL of water
  3. extractionThe aqueous mixture was then extracted 4 times with 50 mL of chloroform
  4. dry with materialThe combined organic phases were dried over anhydous Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-cbf54096069740ad8a43926cd92001ce
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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