Hydrochloric Acid → 7-Methylquinolin-6-ol

HRID 1890920Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[N:8]=[CH:7][CH:6]=[CH:5]2.[OH-:13].[K+].O.Cl>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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O1CCOCC1>[CH3:12][C:11]1[CH:10]=[C:9]2[C:4]([CH:5]=[CH:6][CH:7]=[N:8]2)=[CH:3][C:2]=1[OH:13]

Participants

Conditions

Temperature: 100 °C

Procedure

A vial was purged with nitrogen and charged with 6-bromo-7-methyl-quinoline (2.0 g, 9 mmol), grounded KOH (2.02 g, 36 mmol), tris(dibenzylideneacetone)dipalladium(0) (165 mg, 0.18 mmol), and X-Phos (Strem ligand, 343 mg, 0.72 mmol). Water (6 mL) and 1,4-dioxane (6 mL) were added, and the reaction mixture was stirred at 100° C. for 2 h. After cooling to room temperature, the reaction mixture was acidified to pH 5 with 1 N aqueous HCl and extracted with ethyl acetate (2×). The combined organic layers were adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-100% ethyl acetate/hexane afforded 1.37 g of 7-methyl-quinolin-6-ol as a light yellow solid (95% yield): 1H NMR (DMSO-d6) δ 2.34 (s, 3H), 7.12 (s, 1H), 7.32 (dd, 1H), 7.73 (s, 1H), 8.07 (dd, 1H), 8.60 (dd, 1H), 10.1 (broad s, 1H); MS (m/z) 160 [M+H]+.

Workup

customA vial was purged with nitrogen
temperatureAfter cooling to room temperature
extractionextracted with ethyl acetate (2×)
customPurification by flash chromatography on silica gel using a gradient of 0-100% ethyl acetate/hexane

Sources & evidence

ORD record: ord-547723ec7824484ca27d7a160b4e1962
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507489B2

Reaction notes

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