Imidazole → 1-[2-(2-t-Butyldimethylsilyloxymethyl-4-bromophenoxy)ethyl]pyrrolidine

HRID 1387119Notes

Reaction equation

HRID 1387119 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.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1.O>CN(C=O)C>[Si:18]([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]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 211828631-[2-(2-Hydroxymethyl-4-bromophenoxy)ethyl]pyrrolidine

Product 1

HCID 211829811-[2-(2-t-Butyldimethylsilyloxymethyl-4-bromophenoxy)ethyl]pyrrolidineYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (500 mg, 1.67 mmol) 1-[2-(2-hydroxymethyl-4-bromophenoxy)ethyl]pyrrolidine (Part A) in 5.5 mL of anhydrous DMF was added 377 mg of t-butyldimethylsilyl chloride followed by addition of 113 mg of imidazole. The reaction mixture was stirred at room temperature for 30 h. To the reaction was added 6 mL of water. The mixture was extracted with EtOAc (3×60 mL). The combined organic layers were dried over MgSO4 and concentrated to dryness. The residue was azeotroped with xylenes to remove any DMF present. Purification by flash chromatography (silica gel, 3% to 4% [10% conc NH4OH in MeOH]/CH2Cl2) afforded 528 mg (1.27 mmol, 77%) of a yellow oil.

Workup

  1. extractionThe mixture was extracted with EtOAc (3×60 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. concentrationconcentrated to dryness
  4. customThe residue was azeotroped with xylenes
  5. customto remove any DMF present
  6. customPurification by flash chromatography (silica gel, 3% to 4% [10% conc NH4OH in MeOH]/CH2Cl2)

Sources & evidence

ORD record
ord-0881e9517dfc4b2c872fbe778e6833f9
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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