Water → Ethyl 6-chloro-1-(cyanomethyl)-5-methylindole-2-carboxylate

HRID 392084

Reaction equation

HRID 392084 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8]2)=[CH:4][C:3]=1[CH3:16].[H-].[Na+].Cl[CH2:20][C:21]#[N:22].O>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]2[CH2:20][C:21]#[N:22])=[CH:4][C:3]=1[CH3:16]

Participants

7

Reactant 4

HCID 962WaterHCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 21868716Ethyl 6-chloro-5-methyl-1h-indole-2-carboxylate

Product 1

HCID 21868765Ethyl 6-chloro-1-(cyanomethyl)-5-methylindole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 6-chloro-5-methylindole-2-carboxylate (1.5 g, 6.3 mmol) in DMF (30 mL) was added dropwise to a stirred suspension of sodium hydride (60%, 0.39 g, 10 mmol) in DMF (20 mL) at room temperature under Ar. The reaction was then cooled to 0° C. and stirred for 45 min then chloroacetonitrile (0.81 mL, 13 mmol) was added in one portion. The reaction was heated to 75° C. and stirred for 1 h. After allowing to cool to room temperature the mixture was poured into water (200 mL) and with ethyl acetate (3×100 mL). The combined organic extracts were washed with brine (1×100 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave the crude product which was used immediately.

Workup

  1. temperatureThe reaction was heated to 75° C.
  2. stirringstirred for 1 h
  3. temperatureto cool to room temperature the mixture
  4. washThe combined organic extracts were washed with brine (1×100 mL)
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-e3e3b71823754d06b5a96a1267be853d
Source dataset
uspto-grants-2004_10
Patent number
US06800627B1

Linked notes

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