Methyl iodide → 5-Bromo-2-chloro-3-methylquinoline

HRID 2090055Notes

Reaction equation

HRID 2090055 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([Cl:12])=[N:7]2.[Li+].[CH3:14]C([N-]C(C)C)C.IC.[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH3:14])[C:6]([Cl:12])=[N:7]2

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 142210335-Bromo-2-chloroquinoline

Product 1

HCID 583494715-Bromo-2-chloro-3-methylquinoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-2-chloroquinoline (1.0 g, 4.1 mmol) in anhydrous THF (20 mL) at −78° C. was added LDA (2.0 M in heptane/THF/ethylbenzene, 3.1 mL, 6.2 mmol) dropwise. After stirring for one hour, iodomethane (1.28 mL, 20.6 mmol) was added, and the mixture was stirred at −78° C. for another hour. The mixture was poured into saturated NH4Cl (aq) then extracted twice with EtOAc. The organic extracts were concentrated and the residue was purified by reverse-phase HPLC to afford the title compound: 1H NMR (500 MHz, CDCl3): δ 8.34 (s, 1H); 7.96 (d, J=8.3 Hz, 1H); 7.80 (d, J=7.5 Hz, 1H); 7.53 (d, J=7.8 Hz, 1H); 2.60 (s, 3H) LC3: 1.41 min. (M+H) 258.

Workup

  1. stirringthe mixture was stirred at −78° C. for another hour
  2. extractionthen extracted twice with EtOAc
  3. concentrationThe organic extracts were concentrated
  4. customthe residue was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-9839876bbf954a24818b77e713373f80
Source dataset
uspto-grants-2013_05
Patent number
US08436015B2

Reaction notes

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