Pyridine → 2-chloro-1-phenyl-1H-indole-3-carbaldehyde

HRID 1678104Notes

Reaction equation

HRID 1678104 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]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[N:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 66827Phenylboronic AcidHCID 3147912-chloro-1H-indole-3-carbaldehyde

Product 1

HCID 3147932-chloro-1-phenyl-1H-indole-3-carbaldehydeYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-chloro-1H-indole-3-carboxaldehyde (5.00 g, 27.8 mmol), phenylboronic acid (6.79 g, 55.6 mmol), cupric acetate (10.11 g, 55.7 mmol), pyridine (4.40 g, 55.7 mmol), triethylamine (5.63 g, 55.6 mmol), 4 Å molecular sieves (15.0 g) dichloromethane (300 mL) is stirred at room temperature for 4 d. The reaction mixture is filtered through a pad of Celite and the filtrate is washed with water, with 2N aq hydrochloric acid, with sat aq sodium bicarbonate, with brine, dried, filtered and concentrated. The residue is purified by chromatography eluting with dichloromethane. Product containing fractions are combined and concentrated to afford 2-chloro-1-phenyl-1H-indole-3-carboxaldehyde (4.40 g, 88% yield) as a yellow solid. NMR (CDCl3) 12.30 (1H, s), 8.37 (1H, d), 7.58-7.70 (3H, m), 7.43 (2H, d), 7.23-7.40 (2H, m), 7.10 (1H, d).

Workup

  1. filtrationThe reaction mixture is filtered through a pad of Celite
  2. washthe filtrate is washed with water, with 2N aq hydrochloric acid, with sat aq sodium bicarbonate, with brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by chromatography
  7. washeluting with dichloromethane
  8. additionProduct containing fractions
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-7cd6a3285a6048c4a2831d239999c918
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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