Methyl iodide → 2-(4-Iodo-3-methoxyphenyl)-5,5-dimethyl[1,3]dioxane

Temperature

0 °C

Sodium hydride (887 mg, 60% dispersion in mineral oil, 22.2 mmol) was added to an ice-cooled solution of 3-hydroxy-4-iodobenzaldehyde (5.00 g, 20.2 mmol) in DMF (20 ml) and stirred at 0° C. for 60 min. Iodomethane (3.15 ml, 22.2 mmol) was added dropwise to the solution of the phenolate, and the reaction mixture was stirred at room temperature for 4 h. The mixture was diluted with ethyl acetate and washed with ice-water and saturated sodium chloride solution. After drying over magnesium sulfate, the organic phase was concentrated under reduced pressure. The residue (6.32 g) was dissolved in toluene (150 ml) and, after addition of neopentyl glycol (2.76 g, 26.5 mmol) and Amberlyst-15 (400 mg), the reaction mixture was heated under reflux with a water trap for 3 h. After filtration, the reaction solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (mobile phase gradient 10-25% ethyl acetate in dichloromethane). Yield: 6.83 g (77%) of a yellowish oil. MS (API-ES, pos) m/z=349 [M+H]+

1. stirringthe reaction mixture was stirred at room temperature for 4 h
2. washwashed with ice-water and saturated sodium chloride solution
3. dry with materialAfter drying over magnesium sulfate
4. concentrationthe organic phase was concentrated under reduced pressure
5. dissolutionThe residue (6.32 g) was dissolved in toluene (150 ml)
6. temperaturethe reaction mixture was heated
7. temperatureunder reflux with a water trap for 3 h
8. filtrationAfter filtration
9. concentrationthe reaction solution was concentrated under reduced pressure
10. customthe residue was purified by chromatography on silica gel (mobile phase gradient 10-25% ethyl acetate in dichloromethane)

ORD record

ord-b7362b394e8844ba907dad3d00a32f20

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691815B2