Benzyl Bromide → Tert-butyl 4-(benzyloxy)phenethylcarbamate

HRID 339788Notes

Reaction equation

HRID 339788 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[OH:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:18][CH:17]=1>CC(C)=O>[C:27]([O:26][C:25](=[O:31])[NH:24][CH2:23][CH2:22][C:19]1[CH:18]=[CH:17][C:16]([O:15][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:21][CH:20]=1)([CH3:28])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 11566085Tert-butyl 4-(benzyloxy)phenethylcarbamateYield 87.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a suspension of potassium carbonate (K2CO3; 1.4 grams (g), 10.11 millimole (mmol)) in acetone (40 milliliters (mL)) was added bromomethylbenzene (1.73 g, 10.11 mmol) and tert-butyl 2-(4-hydroxyphenyl)ethylcarbamate (2 g, 8.4 mmol). The reaction mixture was heated at reflux for 15 hours (h) and then concentrated in vacuo. The residue was partitioned between diethyl ether (Et2O) and water (H2O), and the organic fraction was washed with brine, dried over sodium sulfate (Na2SO4), suction filtered, and concentrated in vacuo. The residue was purified by silica gel (SiO2) flash chromatography with 25% Et2O in hexane to afford [2-(4-benzyloxyphenyl)-ethyl]-carbamic acid tert-butyl ester as a white solid (2.4 g). This was dissolved in CH2Cl2 (50 mL) and trifluoroacetic acid (5 mL) was added. After stirring 16 h, the solvent was removed in vacuo, and the residue was redissolved in CH2Cl2, washed with 1M sodium hydroxide (NaOH), dried (Na2SO4) and filtered. The solvent was removed in vacuo to yield 2-(4-benzyloxyphenyl)-ethylamine (1.5 g). This was used without purification in the next step.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 15 hours (h)
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between diethyl ether (Et2O) and water (H2O)
  5. washthe organic fraction was washed with brine
  6. dry with materialdried over sodium sulfate (Na2SO4), suction
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel (SiO2) flash chromatography with 25% Et2O in hexane

Sources & evidence

ORD record
ord-744ad6a851254ddca849d5365d4ee4f9
Source dataset
uspto-grants-2014_11
Patent number
US08895568B2

Reaction notes

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