Bromoacetonitrile → Ethyl 1-(Cyanomethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

HRID 1026396Notes

Reaction equation

HRID 1026396 reaction equation
[NH:1]1[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[H-].[Na+].Br[CH2:18][C:19]#[N:20]>CN(C=O)C>[C:19]([CH2:18][N:1]1[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11])#[N:20]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydride2×HCID 300702ethyl 4,5,6,7-tetrahydro-1H-indole-2-carboxylate

Product 1

HCID 58043903Ethyl 1-(Cyanomethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 125-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with ethyl 4,5,6,7-tetrahydro-1H-indole-2-carboxylate 104g (5.76 g, 29.8 mmol) and DMF (50 mL). The solution was cooled to 0° C. using an ice bath. Sodium hydride, NaH (60% dispersion in mineral oil, 1.43 g, 35.8 mmol) was added. The resulting mixture was stirred at room temperature for 1 h. After that time, bromoacetonitrile (1.43 g, 35.8 mmol) was added. The mixture was stirred at room temperature for 14 h. After that time, the reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (150 mL) and water (450 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 55% yield (3.80 g) of 104h as a yellow semi-solid: 1H NMR (300 MHz, CDCl3) δ 6.66 (s, 1H), 5.29 (s, 2H), 4.28 (q, 2H, J=7.2 Hz), 2.62 (t, 2H, J=6.3 Hz), 2.49 (t, 2H, J=6.3 Hz), 1.92 (m, 2H), 1.75 (m, 2H), 1.33 (t, 3H, J=7.2 Hz); MS (ESI+) m/z 233.1 (M+H)

Workup

  1. customA 125-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
  2. customwas purged with nitrogen
  3. stirringThe mixture was stirred at room temperature for 14 h
  4. concentrationAfter that time, the reaction mixture was concentrated under reduced pressure
  5. customthe residue was partitioned between ethyl acetate (150 mL) and water (450 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×150 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-43f097794d144b5b8c4343b6080339bd
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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