Triethylamine → 8-(4-Bromobenzyl)-8-aza-bicyclo[3.2.1]octan-3-one

HRID 1505941Notes

Reaction equation

HRID 1505941 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Br)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:17]12[NH:24][CH:21]([CH2:22][CH2:23]1)[CH2:20][C:19](=[O:25])[CH2:18]2>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:24]2[CH:17]3[CH2:23][CH2:22][CH:21]2[CH2:20][C:19](=[O:25])[CH2:18]3)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 685274-Bromobenzyl bromideHCID 4344538-Azabicyclo(3.2.1)octan-3-one

Product 1

HCID 551064698-(4-Bromobenzyl)-8-aza-bicyclo[3.2.1]octan-3-oneYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 1-bromo-4-bromomethylbenzene (0.39 g, 1.56 mmol), triethylamine (0.45 mL, 3.20 mmol) and 8-azabicyclo[3.2.1]octan-3-one (0.33 mL, 2.32 mmol) in THF (10 mL) was heated under reflux for 5 h. The reaction mixture was allowed to cool to ambient temperature and the solid removed by filtration. The filtrate was concentrated under reduced pressure to afford a residue that was purified by flash chromatography (silica, 50 g column, Biotage, 0-100% DCM in ethyl acetate) to afford the title compound as an off-white solid (400 mg, 90%). 1H NMR (CDCl3, 300 MHz): 7.48-7.43 (m, 2H), 7.32-7.28 (m, 2H), 3.69 (s, 2H), 3.49-3.43 (m, 2H), 2.66 (dd, J=16.0, 4.3 Hz, 2H), 2.26-2.17 (m, 2H), 2.14-2.06 (m, 2H), 1.66-1.56 (s, 2H). LCMS (Method B): RT=1.86 min, M+H+=294/296.

Workup

  1. temperatureunder reflux for 5 h
  2. customthe solid removed by filtration
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto afford a residue that
  5. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-100% DCM in ethyl acetate)

Sources & evidence

ORD record
ord-935a50bbcd244d348a745a4a9f7a26c8
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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