Pyridine → 1-(4-tert-butylphenyl)-2-chloro-1H-indole-3-carboxaldehyde

HRID 1678151Notes

Reaction equation

HRID 1678151 reaction equation
[Cl:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[C:13]([C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14].N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:13]([C:17]1[CH:22]=[CH:21][C:20]([N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]([CH:11]=[O:12])=[C:2]2[Cl:1])=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 3

HCID 1049PyridineHCID 3147912-chloro-1H-indole-3-carbaldehydeHCID 27343204-tert-Butylphenylboronic acid

Product 1

HCID 860359201-(4-tert-butylphenyl)-2-chloro-1H-indole-3-carboxaldehydeYield 81%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-chloro-1H-indole-3-carboxaldehyde (2.2 g, 12. 25 mmol), 4-t-butylphenylboronic acid (4.36 g, 24.49 mmol), copper acetate (4.45 g, 24.50 mmol), 4A molecular sieve (2.5 g), pyridine (3.0 mL) and dichloromethane (40 mL) is stirred overnight at room temperature. The reaction mixture is diluted with dichloromethane (100 mL), washed with water (50 mL), with 3N aqueous hydrochloric acid (10 mL), the precipitate removed by filtration and the dichloromethane layer is washed again with water (50 mL), aq sodium bicarbonate, with brine, dried and filtered. The filtrate is concentrated to give a solid. The crude is crystallized from dichloromethane-methanol to afford 1-(4-tert-butylphenyl)-2-chloro-1H-indole-3-carboxaldehyde (3.09 g, 81% yield) as a yellow solid. TLC (silica gel, 20% ethyl acetate/heptane) Rf=0.50; ESI/MS 312 (M+H), RT 4.32 min; NMR: 10.12 (1H, s); 8.20 (1H, d, J=6 Hz); 7.71 (2H, d); 7.53 (2H, d); 7.38 (2H, m); 7.11 (1H, d); 1.38 (9H, s).

Workup

  1. washwashed with water (50 mL), with 3N aqueous hydrochloric acid (10 mL)
  2. customthe precipitate removed by filtration
  3. washthe dichloromethane layer is washed again with water (50 mL), aq sodium bicarbonate, with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated
  7. customto give a solid
  8. customThe crude is crystallized from dichloromethane-methanol

Sources & evidence

ORD record
ord-ed8621fd087943288da6e7fc0c7f3e07
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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