Diisobutylaluminum hydride → 6-Chloro-2,2-dimethylchroman-8-carbaldehyde

Temperatur

-78 °C

6-Chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carboxylate (350 mg, 1.37 mmol) was dissolved in dichloromethane (6.87 mL) and cooled to −78° C. DIBAL-H (4.12 mL, 4.12 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour. It was then cooled to 0° C., diluted with dichloromethane (10.0 mL) and water (2.00 mL) was added slowly, followed by a 15% aqueous NaOH solution (5.00 mL). The mixture was warmed to room temperature and stirred for 15 minutes. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under vacuum. The crude alcohol was used directly in the next step without further purification. The crude alcohol was dissolved in dichloromethane (7.00 mL), and Dess-Martin periodinane (1.20 g, 2.75 mmol) was added in one portion at room temperature. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under vacuum on silica gel. It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a white solid.

1. temperatureThe reaction mixture was warmed to room temperature
2. temperatureIt was then cooled to 0° C.
3. additionwas added slowly
4. temperatureThe mixture was warmed to room temperature
5. stirringstirred for 15 minutes
6. customThe organic layer was separated
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customThe crude alcohol was used directly in the next step without further purification
11. dissolutionThe crude alcohol was dissolved in dichloromethane (7.00 mL)
12. stirringThe reaction mixture was stirred at room temperature for 30 minutes
13. concentrationconcentrated under vacuum on silica gel
14. customIt was then purified by silica gel chromatography
15. washeluting with 0-15% EtOAc/hexanes

ORD-Eintrag

ord-eb00497ab7304ad08319006f22f0e54f

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08742110B2