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

HRID 18203Notes

Reaction equation

HRID 18203 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, 11.0M 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-55fbe934d8a74cd6b9e6c6970ad960a3
Source dataset
uspto-grants-2010_06
Patent number
US07741349B2

Reaction notes

Loading…