Reaction #607477

Reaction equation

3

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

hydrochloric acid

ethyl acetate

→

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

Yield 71.0%

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

Yield 71.0%

Solvents

ethanol

Conditions

Workup

1. 1
   OtherA 200-mL Parr reactor bottle was purged with nitrogen
2. 2
   Otherevacuated
3. 3
   workup.ADDITIONcharged with hydrogen gas to a pressure of 50 psi
4. 4
   OtherAfter this time, the hydrogen was evacuated
5. 5
   workup.ADDITIONnitrogen was charged into the bottle
6. 6
   Filtrationdiatomaceous earth filter agent (CELITE®, Imerys Minerals California, Inc.) CELITE® 521 (4.0 g)
7. 7
   workup.ADDITIONwas added
8. 8
   Filtrationthe mixture was filtered through a pad of CELITE® 521
9. 9
   WashThe filter cake was washed with ethanol (2×20 mL)
10. 10
    Concentrationthe combined filtrates were concentrated to dryness under reduced pressure
11. 11
    OtherThe residue was partitioned between ethyl acetate (150 mL) and 10% aqueous potassium carbonate (100 mL)
12. 12
    OtherThe organic layer was separated
13. 13
    Extractionthe aqueous layer was extracted with ethyl acetate (3×75 mL)
14. 14
    DryingThe combined organic layers were dried over sodium sulfate
15. 15
    Concentrationconcentrated under reduced pressure
16. 16
    OtherThe residue was triturated with ethanol (5 mL)

Procedure

A 200-mL Parr reactor bottle was purged with nitrogen and charged with 10% palladium on carbon (50% wet, 1.28 g dry weight), 3 (3.00 g, 12.9 mmol), 12% hydrochloric acid (6.5 mL, 25 mmol), ethyl acetate (60 mL) and ethanol (40 mL). The bottle was attached to a Parr hydrogenator, evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 6 h. After this time, the hydrogen was evacuated, and nitrogen was charged into the bottle. diatomaceous earth filter agent (CELITE®, Imerys Minerals California, Inc.) CELITE® 521 (4.0 g) was added, and the mixture was filtered through a pad of CELITE® 521. The filter cake was washed with ethanol (2×20 mL), and the combined filtrates were concentrated to dryness under reduced pressure. The residue was partitioned between ethyl acetate (150 mL) and 10% aqueous potassium carbonate (100 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×75 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was triturated with ethanol (5 mL) to afford a 71% yield (1.71 g) of ethyl 1-(2-aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate 4 as a white solid: mp 102-104° C.; 1H NMR (500 MHz, DMSO-d6) δ 6.61 (s, 1H), 6.22 (br, 2H), 4.15 (m, 4H), 2.77 (m, 2H), 2.59 (t, 2H, J=6.5 Hz), 2.42 (t, 2H, J=6.5 Hz), 1.70 (m, 2H), 1.62 (m, 2H), 1.23 (t, 3H, J=7.0 Hz); MS (APCI+) m/z 237.2 (M+H)

Source