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

HRID 1411450Notes

Reaction equation

HRID 1411450 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), 101c (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 101d 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. filtrationdiatomaceous earth filter agent (CELITE®, Imerys Minerals California, Inc.) CELITE® 521 (4.0 g)
  7. additionwas added
  8. filtrationthe mixture was filtered through a pad of CELITE® 521
  9. washThe filter cake was washed with ethanol (2×20 mL)
  10. concentrationthe combined filtrates were concentrated to dryness under reduced pressure
  11. customThe residue was partitioned between ethyl acetate (150 mL) and 10% aqueous potassium carbonate (100 mL)
  12. customThe organic layer was separated
  13. extractionthe aqueous layer was extracted with ethyl acetate (3×75 mL)
  14. dry with materialThe combined organic layers were dried over sodium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was triturated with ethanol (5 mL)

Sources & evidence

ORD record
ord-38a330834c6447a1b1c04c3590b7c53f
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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