Triethylamine → tert-Butyl 4-[(3-bromophenyl)methyl]piperazine-1-carboxylate

HRID 2080311Notes

Reaction equation

HRID 2080311 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5]Br.[C:10]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:5][N:20]2[CH2:19][CH2:18][N:17]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:22][CH2:21]2)[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 699793-Bromobenzyl bromideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 53439212tert-Butyl 4-[(3-bromophenyl)methyl]piperazine-1-carboxylateYield 89.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-bromobenzyl bromide (6 g) and Boc-piperazine (4.06 g) in acetonitrile (30 mL) was treated with triethylamine (3.36 mL). The resulting mixture was heated at reflux for 16 hours. After cooling to room temperature, the reaction mixture was treated with saturated sodium bicarbonate solution (20 mL), and then extracted with ethyl acetate (2×30 mL). The organic phases were combined, dried (MgSO4) and concentrated under vacuum. The residue was purified by chromatography on silica (100 g) eluting with ethyl acetate/cyclohexane to give the title compound (6.95 g). LC/MS: m/z, 355, 357 (M+H), 2.40 min.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 16 hours
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by chromatography on silica (100 g)
  7. washeluting with ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-fca5d91c9e904a32ac6bd6a954f349c8
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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