Hydrochloric Acid → 2,3,4,5-Tetrahydro-1-benzoxepine-8-carbaldehyde

To a solution of 2.01 g (8.8 mmol) of 8-bromo-2,3,4,5-tetrahydro-1-benzoxepine in 54 mL of anhydrous tetrahydrofuran and 13.5 mL of hexane under nitrogen cooled in a dry ice/acetone bath was added dropwise 4.1 mL (10.2 mmol, 1.15 equiv) of 2.5M n-butyllithium in tetrahydrofuran, keeping the internal temperature <−65° C. The mixture was stirred with cooling for 45 minutes. A solution of 1.03 mL (13.3 mmol, 1.5 equiv) dimethylformamide in 9 mL of anhydrous tetrahydrofuran was added dropwise over 5 minutes. The mixture was stirred overnight while warming to ambient temperature. The reaction mixture was poured into 81 mL of 2N HCl, and the layers were separated. The aqueous layer was extracted with 3×85 mL of ether. The combined organic layer was washed with 75 mL each of water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 1.64 g of a yellow oil. Purification by flash chromatography (5-40% ethyl acetate in hexanes) gave the product as a colorless oil. MS (m+1)=177.2; 1H NMR (400 MHz, CDCl3) 9.92 (s, 1H), 7.49 (m, 2H), 7.29 (d, 1H, J 7.5 Hz), 4.03 (m, 2H), 2.89 (m, 2H), 2.00 (m, 2H), 1.76 (m, 2H).

1. customthe internal temperature <−65° C
2. temperaturewith cooling for 45 minutes
3. stirringThe mixture was stirred overnight
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with 3×85 mL of ether
6. washThe combined organic layer was washed with 75 mL each of water and brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-7b537d976a674fb18f4725fd43477f30

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07855201B2