4-Chlorobenzylamine → HCID 10109567, compound

HRID 411197Notes

Reaction equation

HRID 411197 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]=[C:6]([CH:12]=[O:13])[C:5]2=[O:14].BrN1[C:20](=[O:21])[CH2:19][CH2:18]C1=O.[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1>C(Cl)(Cl)(Cl)Cl>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:29][C:12]([C:6]2[C:5](=[O:14])[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:18]#[C:19][CH2:20][OH:21])[CH:3]=3)[O:8][CH:7]=2)=[O:13])=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 660364-ChlorobenzylamineHCID 67184N-bromobutanimideHCID 6143096-Bromo-3-formylchromone

Product 1

HCID 10109567HCID 10109567, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

A mixture of 6-bromo-3-formylchromone (1.2 g) and N-bromosuccinimide (0.82 g) in carbon tetrachloride (30 mL) is irradiated with a sun lamp (625 watt) for 20 minutes. The cooled reaction is then treated with 4-chlorobenzylamine (2 mL) and stirred 30 minutes. The resulting amide intermediate is purified by chromatography on silica gel 60 in ethyl acetate/CH2Cl2 mixtures and then recrystallized from CH2Cl2/hexane. (54%, M.p. 182-183° C.) A portion of the resulting amide (0.2 g) in dioxane is combined under argon with bis(benzonitrile) palladium (II) chloride (6 mg), copper(I) iodide (4 mg), a 0.5 M solution of tri-t-butylphosphine in cyclohexane (0.064 mL), diisopropylamine (0.085 mL), and propargyl alcohol (0.037 mL). The reaction is stirred at room temperature overnight. The mixture is diluted with ethyl acetate and filtering. The crude product is purified by column chromatography on silica gel 60 in ethyl acetate/CH2Cl2 mixtures and is then crystallized from methanol/CH2Cl2/ethyl acetate to afford the title compound (23%). Physical characteristics: m.p. 185-186° C. 1H NMR (CDCl3) δ 1.95, 4.52,4.62, 7.30, 7.50, 7.75, 8.27, 8.98, 9.63; MS (ESI) [M+Na]+ 390.

Workup

  1. customis irradiated with a sun lamp (625 watt) for 20 minutes
  2. customThe cooled reaction
  3. customThe resulting amide intermediate is purified by chromatography on silica gel 60 in ethyl acetate/CH2Cl2 mixtures
  4. customrecrystallized from CH2Cl2/hexane
  5. stirringThe reaction is stirred at room temperature overnight
  6. additionThe mixture is diluted with ethyl acetate
  7. filtrationfiltering
  8. customThe crude product is purified by column chromatography on silica gel 60 in ethyl acetate/CH2Cl2 mixtures
  9. customis then crystallized from methanol/CH2Cl2/ethyl acetate

Sources & evidence

ORD record
ord-ffac68f8812441e2a858d2e58fe1a6b9
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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