Chlorotrimethylsilane → 2-Bromo-1-(4-(piperidin-1-yl)phenyl)ethanone

HRID 643959Notes

Reaction equation

HRID 643959 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH3:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl[Si](C)(C)C.[Br:31]NC(=O)CCC(N)=O>C1COCC1.C(OCC)(=O)C>[Br:31][CH2:14][C:13]([C:10]1[CH:11]=[CH:12][C:7]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:8][CH:9]=1)=[O:15]

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 825614'-PiperidinoacetophenoneHCID 2733832Lithium HexamethyldisilazideHCID 9834204N-Bromosuccinamide

Product 1

HCID 158645462-Bromo-1-(4-(piperidin-1-yl)phenyl)ethanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4′-Piperidinoacetophenone (203 mg, 1.00 mmol) was dissolved in THF (5 mL) and treated with lithium bis(trimethylsilyl)amide (1.10 mL, 1.0 M in THF, 1.10 mmol). The solution was stirred for 30 minutes prior to the addition of chlorotrimethylsilane (140 μL, 1.10 mmol). After stirring for an additional 30 minutes N-bromosuccinamide (300 mg, 1.73 mmol) was added and the mixture was refluxed from 4 hours. Standard aqueous/ethyl acetate workup provided a yellow solid which was further purified by silica gel chromatography, eluting with 3:1 hexane/ethyl acetate, to provide 2-bromo-4′-piperidinoacetophenone as an off white solid (209 mg, 74%). 1H NMR (200 MHz, CDCl3) δ 8.75 (d, 2H), 6.84 (d, 2H), 4.61 (s, 2H), 3.40 (m, 4H), 1.68 (m, 6H).

Workup

  1. additionwas added
  2. temperaturethe mixture was refluxed from 4 hours
  3. customwas further purified by silica gel chromatography
  4. washeluting with 3:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-b54eb9dab072452286c6bce16ba2b8d0
Source dataset
uspto-grants-2010_04
Patent number
US07700635B2

Reaction notes

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