Benzyl Chloride → HCID 10454683, compound

HRID 71035Notes

Reaction equation

HRID 71035 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([N:14]([CH3:16])[CH3:15])=[O:13].[H-].[Na+].[H][H].[CH2:21](Cl)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C=O)C>[CH2:21]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([I:1])=[CH:10][CH:9]=2)[C:5]([CH2:11][C:12]([N:14]([CH3:15])[CH3:16])=[O:13])=[CH:6]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 102459112-(5-iodo-1H-indol-3-yl)-N,N-dimethyl-acetamideHCID 178418361HCID 178418361, compound

Product 1

HCID 10454683HCID 10454683, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(5-Iodo-1H-indol-3-yl)-N,N-dimethyl-acetamide (24.7 g, 75.4 mmol) in DMF (90 mL), under an inert atmosphere sodium hydride (1.91 g 95%, 75.4 mmol) is added which leads to the formation of a pale yellow solution. When the evolution of hydrogen has ceased, benzyl chloride (9.54 g, 75.4 mmol) is added in three portions over a period of 10 minutes. The mixture warms to 60° C., and after stirring for one hour a suspension forms. On the rotavapor, a part of the DMF (about 80 mL) is removed, which leads to crystallization of the product. Water (300 mL) is added, and the crystallized product is triturated at 80° C. for one hour on the rotavapor. The product is filtered off, washed twice with water (200 mL each washing), and dried to give 26.8 g (85%) of the title compound as pale yellow crystals, mp=167-168° C. From the mother liquor, another crop (2.6 g, 8%) is obtained which is also pure. 1H-NMR (DMSO-D6, 300 MHz) δ 3.33, 3.72 (2 s, 3H each, N(CH3)2); 3.72 (s, 2H, CH2CO); 5.34 (CH2Ph); 7.08-7.15, 7.15-7.30 (2 m, 5H, Ph); 7.24 (d, 3J=8.7 Hz, H-7); 7.26 (s, 1H, H-2); 7.32 (dd, 4J=1.3 Hz, H-6); 7.94 (d, 1H, H-4). 13C-NMR (DMSO-D6, 75 MHz) δ 30.90 (CH2CO); 35.72, 37.89 (N(CH3)2); 49.70 (CH2Ph); 83.31 (C-5); 108.61 (C-3); 113.26 (C-2); 127.65 (2 Ph-C); 128.06 (C-6 or Ph C-4); 128.53 (C-4); 129.19 (Ph C-4 or C-6); 129.22 (2 Ph-C); 129.83 (C-7); 131.38 (Ph ipso-C); 135.79 (C-9); 138.67 (C-8); 170.82 (CONMe2).

Workup

  1. customwarms to 60° C.
  2. customOn the rotavapor, a part of the DMF (about 80 mL) is removed
  3. customwhich leads to crystallization of the product
  4. additionWater (300 mL) is added
  5. customthe crystallized product is triturated at 80° C. for one hour on the rotavapor
  6. filtrationThe product is filtered off
  7. washwashed twice with water (200 mL each washing)
  8. customdried

Sources & evidence

ORD record
ord-1a4d163d16be44f4b576afe250417395
Source dataset
uspto-grants-2014_09
Patent number
US08822702B2

Reaction notes

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