Hydrochloric Acid → 1,3-Benzodioxole-5-carboxaldehyde, 4-methyl-

n-BuLi (2.5 M in THF, 26.4 mL, 66 mmol) was added dropwise to a solution of N,N,N′-(trimethyl)ethylenediamine (8.6 mL, 6.79 g, 66.4 mmol) in THF (120 mL) at −78° C. (acetone-dry ice bath). After 15 min, piperonal (9.0 g, 60 mmol) was added, the mixture was stirred for 15 min, and n-BuLi (2.5 M in THF, 72 mL, 180 mmol) was added via syringe. After the reaction mixture was stirred for 1 h at −78° C., CH3I (22.4 mL, 50.92 g, 360 mmol) was added at −78° C. The mixture was stirred for 2 h at room temperature, poured into cold stirred 10% hydrochloric acid (prepared with 100 mL concentrated hydrochloric acid and 360 mL water), extracted with CHCl3 (400 mL×3), washed with brine (400 mL), dried (Na2SO4), filtered and concentrated to give the crude product. Purification by preparative flash chromatography (SiO2, EtOAc-hexane 10:1) gave the white crystalline product (6.71 g, 68.1%): mp 70-71° C. 1H NMR (300 MHz, CDCl3) δ 9.96 (s, 1H), 7.34 (d, J=8.1 Hz, 1H), 6.78 (d, J=8.1 Hz, 1H), 6.04 (s, 2H), 2.50 (s, 3H).

1. stirringAfter the reaction mixture was stirred for 1 h at −78° C.
2. stirringThe mixture was stirred for 2 h at room temperature
3. additionpoured
4. extractionextracted with CHCl3 (400 mL×3)
5. washwashed with brine (400 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give the crude product
10. customPurification by preparative flash chromatography (SiO2, EtOAc-hexane 10:1)

ORD record

ord-4dd0add5d9b6429bb90bf47bf477fc3a

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206193B2