94956-98-6

pale brown oil

The synthesis of 2-allyl-3-methoxybenzaldehyde: 3-Methoxybenzyl alcohol 20 was protected as the TBDMS derivative and ortho-allylated (20 → 21 → 22). Deprotection and Swern oxidation gave 2-allyl-3-methoxybenzaldehyde (24) (22 → 23 → 24) [1].
To a cooled (-78 °C) and stirred solution of oxalyl chloride (4012 g, 31.61 mol) in dichloromethane (30 L) was added slowly a solution of dimethyl sulfoxide (4733 g, 60.58 mol) dissolved in 5 L of dichloromethane under argon. After being stirred for 30 min, a solution of 2-allyl-3-methoxybenzyl alcohol (23) (4694 g, 26.34 mol) dissolved in 5 L of dichloromethane was added to this reaction mixture. After the solution was stirred for 1 h at -78 °C, triethylamine (13327 g, 131.70 mol) was added to quench the reaction. The reaction mixture was allowed to warm to room temperature overnight, washed with saturated NH₄Cl and brine, dried (Na₂SO₄), and filtered. The solvent was removed in vacuo to yield a dark brown oil that was chromatographed on silica gel with a solvent gradient of 0–20% ethyl acetate in hexane to yield 3997 g (92% pure by GC, 80% yield) of 2-allyl-3-methoxybenzaldehyde (24) as a pale brown oil.

[1] Moriarty, R. M., Rani, N., Enache, L. A., Rao, M. S., Batra, H., Guo, L., Penmasta, R. A., Staszewski, J. P., Tuladhar, S. M., Prakash, O., Crich, D., Hirtopeanu, A., Gilardi, R. (2004). The Intramolecular Asymmetric Pauson−Khand Cyclization as a Novel and General Stereoselective Route to Benzindene Prostacyclins: Synthesis of UT-15 (Treprostinil). The Journal of Organic Chemistry, 69 6, 1890–1902. https://doi.org/10.1021/jo0347720