4-Chloroindole → 4-Chloroindoline

HRID 1910096Notes

Reaction equation

HRID 1910096 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.C([BH3-])#N.[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][NH:6]2

Participants

5

Reactant 2

HCID 913454-ChloroindoleHCID 5003444Sodium cyanoborohydride

Product 1

HCID 30163064-ChloroindolineYield 78.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
12 °C

Procedure

To a stirred solution of 4-chloroindole (5 g, 33.0 mmol) in Acetic Acid (50 mL) at 12° C. under nitrogen was added sodium cyanoborohydride (6.84 g, 109 mmol) portionwise. The reaction was stirred at 12° C. for 2 hours. LCMS indicated complete conversion, so the reaction mixture was diluted with water (300 mL), cooled in an ice-bath and quenched with sodium hydroxide pellets portionwise until the mixture was strongly basic. The mixture was then extracted with diethyl ether (3×200 mL) and the combined organics dried over sodium sulfate, concentrated and the residue purified by flash chromatography (0-30% EtOAc in hexanes) to afford 4-chloro-2,3-dihydro-1H-indole (4.0 g) as a colourless oil. LC-MS (ES) m/z=154 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.94 (t, J=8.59 Hz, 2H), 3.47 (td, J=8.72, 1.77 Hz, 2H), 5.83 (br. s., 1H), 6.40 (d, J=7.83 Hz, 1H), 6.50 (d, J=8.08 Hz, 1H), 6.90 (t, J=7.96 Hz, 1H).

Workup

  1. temperaturecooled in an ice-bath
  2. customquenched with sodium hydroxide pellets portionwise until the mixture
  3. extractionThe mixture was then extracted with diethyl ether (3×200 mL)
  4. dry with materialthe combined organics dried over sodium sulfate
  5. concentrationconcentrated
  6. customthe residue purified by flash chromatography (0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d4999bfd3c284e008af5abee02585994
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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