Reaction #607476

Reaction equation

2

Ethyl 4,5,6,7-Tetrahydro-1H-indole-2-carboxylate

NaH

bromoacetonitrile

→

ethyl 1-(cyanomethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

Yield 55.0%

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

Yield 55.0%

Solvents

DMF

Conditions

Workup

1. 1
   OtherA 125-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
2. 2
   Otherwas purged with nitrogen
3. 3
   workup.STIRRINGThe mixture was stirred at room temperature for 14 h
4. 4
   ConcentrationAfter that time, the reaction mixture was concentrated under reduced pressure
5. 5
   Otherthe residue was partitioned between ethyl acetate (150 mL) and water (450 mL)
6. 6
   OtherThe organic layer was separated
7. 7
   Extractionthe aqueous layer was extracted with ethyl acetate (3×150 mL)
8. 8
   WashThe combined organic layers were washed with brine
9. 9
   Dryingdried over sodium sulfate
10. 10
    Concentrationconcentrated under reduced pressure
11. 11
    OtherThe residue was purified by column chromatography

Procedure

A 125-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with 2 (5.76 g, 29.8 mmol) and DMF (50 mL). The solution was cooled to 0° C. using an ice bath. 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 ethyl 1-(cyanomethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate 3 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)

Source