Water → Ethyl 6-bromo-1-cyanomethylindole-2-carboxylate

HRID 392080Notes

Reaction equation

HRID 392080 reaction equation
[Br: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][CH:3]=1.[H-].[Na+].Cl[CH2:19][C:20]#[N:21].O>CN(C=O)C>[Br: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[CH2:19][C:20]#[N:21])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 70094966-Bromo-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 21868726Ethyl 6-bromo-1-cyanomethylindole-2-carboxylateYield 95.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 6-bromoindole-2-carboxylate (4.4 g, 16.4 mmol) in DMF (20 mL) was added dropwise over ˜2-3 min to a stirred suspension of sodium hydride (60%, 1.0 g, 25 mmol) in DMF (20 mL) at 0° C. under Ar. The reaction was stirred at 0° C. for 45 min then chloroacetonitrile (2.1 mL, 33 mmol) was added in one portion. The reaction was then heated to 75° C. and stirred for 1 h. After allowing to cool to room temperature the mixture was poured into water (150 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (75 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate) to give the product as a yellow solid (4.8 g, 95%). IR νmax (Nujol)/cm−1 3320, 3089, 2925, 2855, 1898, 1705, 1609, 1530, 1521, 1470, 1449, 1427, 1400, 1394, 1377, 1367, 1336, 1308, 1265, 1205, 1151, 1134,1108, 1054, 1027, 993, 950, 90, 873, 841, 832, 802, 792, 762, 736, 663, 615 and 589; NMR OH (400 MHz; CDCl3) 7.61 (1H, s), 7.57 (1H, d, J.8.5 Hz), 7.37 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5 Hz, 1.5 Hz), 5.57 (2H, s), 4.45 (2H, q, J 7.2 Hz), 1.42 (3H, t, J 7.2 Hz).

Workup

  1. temperatureThe reaction was then heated to 75° C.
  2. stirringstirred for 1 h
  3. temperatureto cool to room temperature the mixture
  4. extractionextracted with ethyl acetate (3×75 mL)
  5. washThe combined organic extracts were washed with brine (75 mL)
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customthe solvent removed under vacuum
  9. customto leave a crude solid which
  10. customwas purified by flash column chromatography (SiO2; ethyl acetate)

Sources & evidence

ORD record
ord-513e9990890a4e679ecc37f5d7b05a5a
Source dataset
uspto-grants-2004_10
Patent number
US06800627B1

Reaction notes

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