Sodium borohydride → 7-chloro-1H-indole

HRID 1371865Notes

Reaction equation

HRID 1371865 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9](=O)[CH2:10]Cl.[BH4-].[Na+]>O1CCOCC1.O>[Cl:8][C:7]1[CH:6]=[CH:5][CH:4]=[C:3]2[C:2]=1[NH:1][CH:10]=[CH:9]2

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 124777781-(2-Amino-3-chlorophenyl)-2-chloroethan-1-one

Product 1

HCID 1046447-chloro-1H-indole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Dissolve 1-(2-amino-3-chlorophenyl)-2-chloroethanone (7.0 g, 34.30 mmol) in 10% aqueous 1,4-dioxane (75 mL). Carefully add NaBH4 (2.6 g, 68.6 mmol, 2 eq.) as a solid. Heat to reflux. After 4 hours, cool to room temperature, dilute with water (300 mL), and extract with dichloromethane (2×200 mL). Combine the organic layers, dry over MgSO4, filter, and remove the solvent in vacuo leaving a light brown oil in the flask. Purify the oil by HPLC (silica gel mobile phase: 100% hexane to 50% EtOAc in hexanes over 50 minutes), to give the title compound as a brown oil: 1H NMR (300 MHz, d6-DMSO-d6): 5.16 (m, 1H), 5.39 (d, 1H), 5.70 (bs, 1H), 6.59 (t, 1H), 7.09 (m, 2H); MS (ES+): m/z 154, 152 (M+H)+.

Workup

  1. temperatureHeat to reflux
  2. extractionextract with dichloromethane (2×200 mL)
  3. dry with materialCombine the organic layers, dry over MgSO4
  4. filtrationfilter
  5. customremove the solvent in vacuo
  6. customleaving a light brown oil in the flask
  7. customPurify the oil by HPLC (silica gel mobile phase: 100% hexane to 50% EtOAc in hexanes over 50 minutes)

Sources & evidence

ORD record
ord-5f4262191c1c49d4b059d8c283e33bd9
Source dataset
uspto-grants-2007_01
Patent number
US07157488B2

Reaction notes

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