Dimethylformamide → 4,4-dimethyl-3,4-dihydro-2H-thiochromene-6-carbaldehyde

Temperature

-78 °C

1-Bromo-4-[(3-methylbut-3-en-1-yl)sulfanyl]benzene (1.05 g, 4.08 mmol) dissolved in dichloromethane (24.0 mL) was cooled to 0° C., and aluminum chloride (0.60 g, 4.49 mmol) was added portionwise. The reaction mixture was stirred at 0° C. for 1 hour and warmed to room temperature for another hour. It was then poured into an Erlenmeyer flask containing a 10% aqueous NaOH solution and ice. The mixture was extracted with dichloromethane (2×, 40.0 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under vacuum. The crude residue was purified by silica gel chromatography eluting with 0-10% EtOAc/Hexanes to give 6-bromo-4,4-dimethyl-3,4-dihydro-2H-thiochromene as a pale-yellow oil. 6-Bromo-4,4-dimethyl-3,4-dihydro-2H-thiochromene (798 mg, 3.10 mmol) in THF (21.0 mL) was cooled to −78° C. and n-BuLi (1.50 mL, 3.72 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 10 minutes and then DMF (961 μl, 12.4 mmol) was added dropwise via a syringe. The resulting mixture was allowed to warm to room temperature and wet silica gel (5.0 g/0.5 mL of water) was added. The mixture was allowed to stir at room temperature for 10 minutes before it was filtered. The silica gel was rinsed with EtOAc and the filtrate was concentrated under vacuum. The crude residue was purified by silica gel chromatography eluting with 0-20% EtOAc/hexanes to obtain the desired product as a pale-yellow oil.

1. temperatureto warm to room temperature
2. additionwet silica gel (5.0 g/0.5 mL of water) was added
3. stirringto stir at room temperature for 10 minutes before it
4. filtrationwas filtered
5. washThe silica gel was rinsed with EtOAc
6. concentrationthe filtrate was concentrated under vacuum
7. customThe crude residue was purified by silica gel chromatography
8. washeluting with 0-20% EtOAc/hexanes

ORD record

ord-7e3f510b6ddd4adc937fb3302bc18de4

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08742110B2