Hydrogen Bromide → methyl 7-hydroxy-3,4-dihydro-2H-chromene-4-carboxylate

Temperature

130 °C

To 7-methoxy-3,4-dihydro-2H-chromene-4-carboxylic acid (0.71 g, 3.41 mmol) was added HBr (0.276 g, 3.41 mmol) and the reaction was heated at 130° C. for 3 hours. The reaction was cooled and concentrated, and the residue was loaded onto a silica gel samplet. The product was eluted using a gradient of 0.5% MeOH/CH2Cl2 containing 0.5% acetic acid to 10% acetic acid/CH2Cl2 containing 0.5% acetic acid. The isolated product was dissolved in MeOH (5 mL) and concentrated sulfuric acid (1 mL) was added and the reaction heated at 75° C. After 2 hours, reaction was cooled, diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography, eluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2, to provide the title compound (0.312 g, 43.9% yield).

1. temperatureThe reaction was cooled
2. concentrationconcentrated
3. washThe product was eluted
4. dissolutionThe isolated product was dissolved in MeOH (5 mL)
5. additionconcentrated sulfuric acid (1 mL) was added
6. temperaturethe reaction heated at 75° C
7. customreaction
8. temperaturewas cooled
9. washwashed with water (25 mL) and brine (25 mL)
10. dry with materialThe organic layer was dried over magnesium sulfate
11. concentrationconcentrated
12. customThe residue was purified by silica gel chromatography
13. washeluting with a gradient of 0.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

ORD record

ord-9e7afcc8b2dd45458207c1bb9ab3d261

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716498B2