Hydrochloric Acid → 2,2-Dimethylchroman-8-carbaldehyde

Temperature

0 °C

2,2-Dimethyl-3,4-dihydro-2H-chromene-8-carboxylic acid (300 mg, 1.45 mmol) dissolved in THF (3.60 mL) was cooled to 0° C. and BH3-THF (5.82 mL, 5.82 mmol) was added dropwise via a syringe. The resulting solution was stirred at 65° C. for 1 hour, and then allowed to cool to room temperature before addition of 6 N HCl (2.50 mL). The mixture was again heated at 65° C. for 30 minutes. The solution was cooled to room temperature, made basic with 1N NaOH and extracted with EtOAc (40.0 mL, 3×). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum to obtain the crude alcohol as a colorless oil, which was directly used to the next step. The crude alcohol was dissolved in dichloromethane (5.00 mL), and Dess-Martin periodinane (1.23 g, 2.91 mmol) was added in one portion at room temperature. The reaction mixture was stirred for 1 hour at room temperature and concentrated under vacuum on silica gel. The crude residue was purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a colorless oil.

1. temperatureThe mixture was again heated at 65° C. for 30 minutes
2. temperatureThe solution was cooled to room temperature
3. extractionextracted with EtOAc (40.0 mL, 3×)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customto obtain the crude alcohol as a colorless oil, which
8. stirringThe reaction mixture was stirred for 1 hour at room temperature
9. concentrationconcentrated under vacuum on silica gel
10. customThe crude residue was purified by silica gel chromatography
11. washeluting with 0-15% EtOAc/hexanes

ORD record

ord-b6f9cb66f5004cd591eebf7f66f5d6d5

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08742110B2