Methyl iodide → 7-Fluoro-2-methylisoquinolin-1(2H)-one

HRID 575561Notes

Reaction equation

HRID 575561 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][NH:10][C:11]2=[O:14])=[CH:6][CH:5]=1.[CH3:15]I.[NH4+].[Cl-]>CN(C=O)C>[F:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][N:10]([CH3:15])[C:11]2=[O:14])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 222501227-Fluoro-1,2-dihydroisoquinolin-1-one

Product 1

HCID 208001207-Fluoro-2-methylisoquinolin-1(2H)-oneYield 50.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under N2, sodium hydride (710 mg, 29.4 mmol) was added to 7-fluoro-2H-isoquinolin-1-one (4 g, 24.55 mmol) in dry DMF (40 mL) at 0° C. After stirring at 0° C. for 20 min, CH3I (5.2 g, 36.7 mmol) was added. The mixture was stirred at 26° C. for 2 h. Saturated aqueous NH4Cl (20 mL) was added and after extractive work up with ethyl acetate, purification by silica gel chromatography (PE:EA=10:1) gave the title compound (2.2 g, 50%) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 8.06 (dd, J1=9.6 Hz, J2=2.8 Hz, 1H), 7.50 (dd, J1=8.8 Hz, J2=5.2 Hz, 1H), 7.38-7.36 (m, 1H), 7.03 (d, J=7.6 Hz, 1H), 6.48 (d, J=7.2 Hz, 1H), 3.61 (s, 3H). LCMS: 178.1 [M+H]+

Workup

  1. stirringThe mixture was stirred at 26° C. for 2 h
  2. customafter extractive work up with ethyl acetate, purification by silica gel chromatography (PE:EA=10:1)

Sources & evidence

ORD record
ord-5e924c0a50584a49ad51262212463e89
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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