Potassium Hydroxide → 4-Benzyloxy-6-methoxy-[1,5]naphthyridin-3-ol

HRID 2279426Notes

Reaction equation

HRID 2279426 reaction equation
[CH2:1]([O:8][C:9]1[C:10](Br)=[CH:11][N:12]=[C:13]2[C:18]=1[N:17]=[C:16]([O:19][CH3:20])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:22]1CCOCC1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[OH-].[K+]>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[N:17]=2)[N:12]=[CH:11][C:10]=1[OH:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 667463738-Benzyloxy-7-bromo-2-methoxy-[1,5]naphthyridine

Product 1

HCID 1363794134-Benzyloxy-6-methoxy-[1,5]naphthyridin-3-olYield 53%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (36 mg, 0.039 mmol, 0.02 eq) is added at room temperature to a stirred solution of 8-benzyloxy-7-bromo-2-methoxy-[1,5]naphthyridine (680 mg, 1.97 mmol, 1.0 eq) in water (10 mL), and dioxane (20 mL), followed by 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (47 mg, 0.099 mmol, 0.05 eq) and a solution of potassium hydroxide (220 mg, 3.94 mmol, 2.0 eq) in water (10 mL). After 6 hours stirring at 90° C., the reaction mixture is quenched with a 1N hydrochloric acid aqueous solution (4 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 4:1, v/v) to afford 4-benzyloxy-6-methoxy-[1,5]naphthyridin-3-ol as a light yellow solid (278 mg, 53% yield).

Workup

  1. customthe reaction mixture is quenched with a 1N hydrochloric acid aqueous solution (4 mL)
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-e85b0115cc92452b83ac7696a37287ee
Source dataset
uspto-grants-2015_09
Patent number
US09133219B2

Reaction notes

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