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

HRID 1843153Notes

Reaction equation

HRID 1843153 reaction equation
[C:1]([CH2:3][N:4]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:6]=[C:5]1[C:13]([O:15][CH2:16][CH3:17])=[O:14])#[N:2].Cl.C(OCC)(=O)C>[Pd].C(O)C>[NH2:2][CH2:1][CH2:3][N:4]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:6]=[C:5]1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 58043903Ethyl 1-(Cyanomethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

Product 1

HCID 58043965Ethyl 1-(2-Aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylateYield 71%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

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), 104h (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. 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 104i 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)

Workup

  1. customA 200-mL Parr reactor bottle was purged with nitrogen
  2. customevacuated
  3. additioncharged with hydrogen gas to a pressure of 50 psi
  4. customAfter this time, the hydrogen was evacuated
  5. additionnitrogen was charged into the bottle
  6. additionCelite 521 (4.0 g) was added
  7. filtrationthe mixture was filtered through a pad of Celite 521
  8. washThe filter cake was washed with ethanol (2×20 mL)
  9. concentrationthe combined filtrates were concentrated to dryness under reduced pressure
  10. customThe residue was partitioned between ethyl acetate (150 mL) and 10% aqueous potassium carbonate (100 mL)
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with ethyl acetate (3×75 mL)
  13. dry with materialThe combined organic layers were dried over sodium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was triturated with ethanol (5 mL)

Sources & evidence

ORD record
ord-69f9fc04dd2548628a573349fbc5b08c
Source dataset
uspto-grants-2015_02
Patent number
US08946213B2

Reaction notes

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