Hydrazine hydrate (1:1) → 4-Chloro-5-benzyloxyindole

HRID 1898983Notes

Reaction equation

HRID 1898983 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[C:4]([N+:16]([O-])=O)[C:3]=1[CH3:19].[CH2:20](OC(OCC)N(C)C)C.N1CCCC1.O.NN>CN(C=O)C.C1COCC1.[Ni].CO>[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[C:4]2[C:3]=1[CH:19]=[CH:20][NH:16]2

Participants

9

Reactant 4

HCID 24654Hydrazine hydrate (1:1)2×HCID 31268PyrrolidineHCID 70913Dimethylformamide diethylacetalHCID 233730582-Chloro-3-benzyloxy-6-nitrotoluene

Product 1

HCID 233731004-Chloro-5-benzyloxyindoleYield 77.2%

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-chloro-3-benzyloxy-6-nitro-toluene (5.00 g, 18.0 mmol) in DMF (25 ml) was added dimethylformamide diethyl acetal (3.14 g, 21.3 mmol) and pyrrolidine (1.51 g, 21.3 mmol), and the mixture was heated at 110° C. for 3 hours under nitrogen. Evaporation under high vacuum at 70° C. gave a deep-red oil which was dissolved in THF (35 ml) and methanol (35 ml) and treated with Raney nickel (0.4 ml) and then hydrazine hydrate (1.30 ml), while stirring at room temperature under nitrogen. The temperature rose to 45° C., and was maintained there by gently warming on an oil bath. A further quantity of hydrazine hydrate (1.30 ml) was added after 30 minutes, and stirring at 45° C. was continued for another hour. The mixture was allowed to cool, filtered through celite, evaporated to a brown oil and purified by chromatography (SiO2 ; C6H14 /CHCl3) to give 4-chloro-5-benzyloxyindole as a yellow oil (3.58 g).

Workup

  1. customEvaporation under high vacuum at 70° C.
  2. customgave a deep-red oil which
  3. customrose to 45° C.
  4. temperaturewas maintained there
  5. temperatureby gently warming on an oil bath
  6. waitwas continued for another hour
  7. temperatureto cool
  8. filtrationfiltered through celite
  9. customevaporated to a brown oil
  10. custompurified by chromatography (SiO2 ; C6H14 /CHCl3)

Sources & evidence

ORD record
ord-0c75df5e624943c28ada08c1d0a44e27
Source dataset
uspto-grants-1996_11
Patent number
US05571833

Reaction notes

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