2,4-Dichlorobenzyl chloride → 861238-35-9

HRID 2106065Notes

Reaction equation

HRID 2106065 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9](/[CH:11]=[CH:12]/[C:13]([NH:15][S:16]([C:19]3[S:20][C:21]([Cl:25])=[C:22]([Cl:24])[CH:23]=3)(=[O:18])=[O:17])=[O:14])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:26].[H-].[Na+].[Cl:29][C:30]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:31]=1[CH2:32]Cl>CN(C=O)C>[Cl:29][C:30]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:31]=1[CH2:32][N:7]1[C:8]2[C:4](=[CH:3][C:2]([F:1])=[CH:10][C:9]=2/[CH:11]=[CH:12]/[C:13]([NH:15][S:16]([C:19]2[S:20][C:21]([Cl:25])=[C:22]([Cl:24])[CH:23]=2)(=[O:17])=[O:18])=[O:14])[C:5]([CH3:26])=[CH:6]1

Participants

5

Reactant 3

HCID 72122,4-Dichlorobenzyl chlorideHCID 24758Sodium hydrideHCID 57810472882999-52-2

Product 1

HCID 11296282861238-35-9Yield 156.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4,5-dichlorothiophene-2-sulfonic acid [(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)-acryloyl]-amide (1.025 kg, 2.37 mole) in DMF (5.1 L) at 0° C. was added NaH (60% in oil, 353 g, 8.8 mole) portionwise and the reaction mixture was allowed to stir for 30 min. 2,4-Dichlorobenzyl chloride (924 g, 1.41 mole) was added at such a rate to maintain the temperature near 0° C. After stirring about 45 min, the reaction mixture was carefully quenched with water (15 L), then diluted with 2 M HCl (9 L) and dichloromethane (10 L), which led to precipitation of the desired title product. The precipitated product was collected via vacuum filtration and the filter cake washed sequentially with water (2×2 L), and cold EtOH (2×1 L). The product was vacuum dried at 60° C. to afford 1.305 kg (93% yield) of desired product, as a solvate with DMF. The product was recrystallized from absolute EtOH to afford the pure product: 1H-NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 5.53 (s, 2H), 6.12 (d, 1H, J=8.4 Hz), 6.21 (d, 1H, J=15.4 Hz), 7.04 (dd, 1H, J=10.0, 2.4 Hz), 7.22 (dd, 1H, J=8.4, 2.0 Hz), 7.37 (s, 1H), 7.38 (d, 1H, J=2.0 Hz), 7.46 (dd, 1H, J=9.2, 2.4 Hz), 7.74 (d, 1H, J=15.4 Hz), 7.90 (s, 1H).

Workup

  1. stirringAfter stirring about 45 min
  2. customthe reaction mixture was carefully quenched with water (15 L)
  3. additiondiluted with 2 M HCl (9 L) and dichloromethane (10 L), which
  4. customled to precipitation of the desired title product
  5. filtrationThe precipitated product was collected via vacuum filtration
  6. washthe filter cake washed sequentially with water (2×2 L), and cold EtOH (2×1 L)
  7. customdried at 60° C.

Sources & evidence

ORD record
ord-04df6f873a0f43de9bde3584b542a847
Source dataset
uspto-grants-2009_08
Patent number
US07579483B2

Reaction notes

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