Benzyl Bromide → 1-[2-(2-Benzyloxymethyl-4-bromophenoxy)ethyl]pyrrolidine

HRID 1387122Notes

Reaction equation

HRID 1387122 reaction equation
[OH:1][CH2:2][C:3]1[CH:16]=[C:15]([Br:17])[CH:14]=[CH:13][C:4]=1[O:5][CH2:6][CH2:7][N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1.[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:20]([O:1][CH2:2][C:3]1[CH:16]=[C:15]([Br:17])[CH:14]=[CH:13][C:4]=1[O:5][CH2:6][CH2:7][N:8]1[CH2:9][CH2:10][CH2:11][CH2:12]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 211828631-[2-(2-Hydroxymethyl-4-bromophenoxy)ethyl]pyrrolidine

Product 1

HCID 211827551-[2-(2-Benzyloxymethyl-4-bromophenoxy)ethyl]pyrrolidineYield 51%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution containing (1.00 g, 3.33 mmol) 1-[2-(2-hydroxymethyl-4-bromophenoxy)ethyl]pyrrolidine (Example 205, Part A) in 65 mL of anhydrous DMF was added 173 mg of NaH (60% dispersion in mineral spirits). The dropwise of addition of (0.40 mL, 3.33 mmol) benzyl bromide and (12.0 mg, 0.0333 mmol) of tetrabutylammonium iodide followed. The reaction was stirred at room temperature, for 1.5 h. The reaction was quenched by the addition of 100 mL of water. The mixture was extracted with EtOAc (3×500 mL). The combined organic layers were washed with brine (1×300 mL) and dried over MgSO4 and concentrated under reduced pressure and azeotroped with xylenes to remove residual DMF. Purification by flash chromatography (silica gel, 3.5% to 5.5% [10% conc NH4OH in MeOH]/CH2Cl2) afforded 660 mg (1.69 mmol, 51%) of a yellow oil.

Workup

  1. customThe reaction was quenched by the addition of 100 mL of water
  2. extractionThe mixture was extracted with EtOAc (3×500 mL)
  3. washThe combined organic layers were washed with brine (1×300 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customazeotroped with xylenes
  7. customto remove residual DMF
  8. customPurification by flash chromatography (silica gel, 3.5% to 5.5% [10% conc NH4OH in MeOH]/CH2Cl2)

Sources & evidence

ORD record
ord-a18c7868d85748c69b6e8967a02c8f82
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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