Water → HCID 178490444, compound

HRID 2289978Notes

Reaction equation

HRID 2289978 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16](I)=[CH:15][C:14]=3[O:22][CH3:23])=[O:9])=[CH:4][CH:3]=1.[CH2:26]([OH:29])[C:27]#[CH:28].O>C(NCC)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([C:28]#[C:27][CH2:26][OH:29])=[CH:15][C:14]=3[O:22][CH3:23])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 962WaterHCID 7859Propargyl alcoholHCID 178492956HCID 178492956, compound

Product 1

HCID 178490444HCID 178490444, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8021DiethylamineSolvent

Procedure

N-(4-Chlorobenzyl)-4-hydroxy-6-iodo-8-methoxy-3-quinolinecarboxamide (469 mg) from Example No. 117, copper (I) iodide (57 mg), and bis(triphenylphosphine)-palladium (II) chloride (35 mg) are suspended in diethylamine (15 mL). Propargyl alcohol (70 μL) is added and the mixture is allowed to stir at rt for 16 h. The reaction mixture is poured into water (50 mL) and extracted with ethyl acetate (2×50 mL). The organic layer is washed with saturated aqueous ammonium chloride (3×10 mL) and brine (10 mL). The aqueous layer is back-extracted with ethyl acetate (20 mL). The combined organic layers are dried (MgSO4) and concentrated. The crude product is purified by column chromatography (dichloromethane/methanol, 50/1; 33/1; 25/1; 20/1) to afford 289 mg (73%) of the title compound as a white solid.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe organic layer is washed with saturated aqueous ammonium chloride (3×10 mL) and brine (10 mL)
  3. extractionThe aqueous layer is back-extracted with ethyl acetate (20 mL)
  4. dry with materialThe combined organic layers are dried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude product is purified by column chromatography (dichloromethane/methanol, 50/1; 33/1; 25/1; 20/1)

Sources & evidence

ORD record
ord-579d124186cd4fb0ad4bc1329b2f5fe6
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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