Water → HCID 59375078, compound

HRID 1810997Notes

Reaction equation

HRID 1810997 reaction equation
[Br:1][C:2]1[C:3]([CH3:19])=[C:4]([NH:8][C:9](=[O:18])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16]Cl)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].O>CN(C=O)C>[Br:1][C:2]1[C:3]([CH3:19])=[C:4]([N:8]2[CH2:16][C:11]3[C:10](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:9]2=[O:18])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24758Sodium hydrideHCID 66606551HCID 66606551, compound

Product 1

HCID 59375078HCID 59375078, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-bromo-2-methylaniline (10 g, 53.7 mmol) in DCM (200 mL) at 0° C. was treated with TEA (14.98 mL, 107 mmol), followed by dropwise addition of 2-(chloromethyl)benzoyl chloride (10.16 g, 53.7 mmol) in DCM (50 mL) over 1 h. The mixture was diluted with DCM (ca. 1 L), washed with NaHCO3 (aq) and water, and concentrated to remove most of the solvent. The precipitate was collected by filtration and washed with DCM (2×10 mL) to provide N-(3-bromo-2-methylphenyl)-2-(chloromethyl)benzamide as a white solid (8.0 g). The filtrate was concentrated further, resulting in additional precipitate which was collected by filtration and washed with DCM (2×10 mL) to provide additional N-(3-bromo-2-methylphenyl)-2-(chloromethyl)benzamide as a white solid (3.06 g), for a combined yield of 61%. Mass spectrum 338, 340, 342 The filtrate was concentrated and purified by column chromatography (hexane-EtOAc) to provide 2-(3-bromo-2-methylphenyl)isoindolin-1-one as a yellow solid (2.0 g, 12%). A solution of the N-(3-bromo-2-methylphenyl)-2-(chloromethyl)benzamide (11.06 g, 32.7 mmol) in DMF (50 mL) was cooled to 0° C. and treated with a mixture of sodium hydride (60% oil dispersion, pre-washed with hexane, 1.70 g, 42.5 mmol) and DMF (10 mL). The mixture was stirred at 0° C. for 1.5 h, then was treated with water. The precipitate was collected by filtration, dried and combined with the material purified by column chromatography (see above) to provide 2-(3-bromo-2-methylphenyl)isoindolin-1-one as a yellow solid (9.41 g, 95%). 1H NMR (400 MHz, chloroform-d) δ 7.96 (1 H, d, J=7.5 Hz), 7.58-7.67 (2 H, m), 7.49-7.57 (2 H, m), 7.20-7.25 (1 H, m), 7.15 (1 H, t, J=7.9 Hz), 4.72 (2 H, s), 2.31 (3 H, s). Mass spectrum m/z 302, 304 (M+H)+.

Workup

  1. filtrationThe precipitate was collected by filtration
  2. customdried
  3. custompurified by column chromatography (see above)

Sources & evidence

ORD record
ord-fa36b65800e248f4b731f7f57396bd03
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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