Chloroacetonitrile → HCID 21868736, compound

HRID 857443Notes

Reaction equation

HRID 857443 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([O:13][CH3:14])=[O:12])[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:18][C:19]#[N:20]>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([O:13][CH3:14])=[O:12])[N:8]2[CH2:18][C:19]#[N:20])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 4715032methyl 6-chloro-1H-indole-2-carboxylate

Product 1

HCID 21868736HCID 21868736, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 6-chloroindole-2-carboxylate (9.8 g, 46.7 mmol) (D. Knittel, Synthesis, 1985, 2, 186–188) in DMF (80 mL) under Ar at ambient temperature was added sodium hydride (60%; 2.80 g, 70 mmol) portionwise over 10 min. After 30 min, chloroacetonitrile (5.9 mL, 93.2 mmol) was added dropwise and the resultant mixture was heated at 75° C. (bath temp.) for 45 min; then allowed to cool. The reaction mixture was poured onto ice (500 mL) and the solid product was filtered, washed with ice-cold water (100 mL), and triturated with refluxing ethanol (150 mL). After allowing to cool to ambient temperature, then cooling in ice, the solid product was filtered-off and washed with ice-cold ethanol (50 mL) to afford the title compound (9.49 g, 82%) as a light grey solid: mp 177–8° C.; IR νmax (Nujol)/cm−1; 3094, 2955, 2925, 2854, 1713, 1613, 1568, 1527, 1519, 1448, 1421, 1398, 1378, 1336, 1306, 1260, 1150, 1108, 1060, 943, 908, 834, 802, 761, 737, 682, 618, 597, 518 and 478; NMR δH (400 MHz, DMSO-d6) 3.95 (3H, s), 5.56 (2H, s), 7.22 (1H, dd, J 8.5, 2 Hz), 7.34 (1H, d, J 1 Hz), 7.43 (1H, br s) and 7.62 (1H, d, J 8.5 Hz).

Workup

  1. temperatureto cool
  2. additionThe reaction mixture was poured onto ice (500 mL)
  3. filtrationthe solid product was filtered
  4. washwashed with ice-cold water (100 mL)
  5. customtriturated with refluxing ethanol (150 mL)
  6. temperaturecooling in ice
  7. washwashed with ice-cold ethanol (50 mL)

Sources & evidence

ORD record
ord-9192bc79772f44639966b92f8ce20d79
Source dataset
uspto-grants-2006_12
Patent number
US07145009B2

Reaction notes

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