Hydrazine hydrate (1:1) → tert-butyl 5-(aminomethyl)-4-chloro-1H-indole-1-carboxylate

HRID 475304Notes

Reaction equation

HRID 475304 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([Cl:29])[C:13]([CH2:17][N:18]3C(=O)C4C(=CC=CC=4)C3=O)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.NN>CCO.O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([Cl:29])[C:13]([CH2:17][NH2:18])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 71272684tert-butyl-4-chloro-5-((1,3-dioxoisoindolin-2-yl)methyl)-1H-indole-1-carboxylate

Product 1

HCID 71272344tert-butyl 5-(aminomethyl)-4-chloro-1H-indole-1-carboxylateYield 73.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred suspension of 318 (10.75 g, 0.026 mol) in EtOH (200 mL) was added hydrazine hydrate (2.52 mL, 0.052 mol), and the resulting reaction mixture was heated at 100° C. for 1 h. The cooled reaction mixture was diluted with water and thrice extracted with DCM. The combined organic layers were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The solid was suspended in hexane (100 mL) and ethyl acetate (5 mL) and filtered. The filtrate was concentrated under reduced pressure to afford 5.34 g (73%) of tert-butyl-5-(aminomethyl)-4-chloro-1H-indol-1-carboxylate (320) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ 7.97 (d, J=8.5 Hz, 1H), 7.73 (s, 1H), 7.50 (d, J=8.5 Hz, 1H), 6.71 (d, J=3.7 Hz, 1H), 2.09 (s, 2H), 1.63 (s, 9H); 2H not seen; MS (ESI) m/z=281.5 [M+1]+.

Workup

  1. customthe resulting reaction mixture
  2. customThe cooled reaction mixture
  3. extractionextracted with DCM
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. filtrationethyl acetate (5 mL) and filtered
  9. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-17b8d29cc8ef44bab74e7fd4ebc816ea
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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