Multikilogram-scale Birch reduction
Birch Reduction is an important reduction reaction in organic chemistry, in particular to reduce aromatic rings. [1] Very recently, A. E. Goetz and Coll. from the Chemical Research and Development at Pfizer (Groton, Connecticut) published a multikilogram-scale Birch reduction of 3-methylanisole to prepare the 7-methyl-1,4-dioxaspiro[4.5]dec-6-ene B (see Scheme below). This reduction was carried out on 50 kg-scale with lithium (this metal reacts violently with water, releasing flammable and explosive H2 gas) and liquid ammonia (a highly corrosive compound with a boiling point of -33°C) in THF at -60 to 50°C to provide the desired intermediate A in 75-80% yield (44.9 kg).
This sequence with the Birch reduction was the most effective route in terms of yield, purity and overall costs. Some safety data relating to this Birch reduction are presented in the Supporting Information.
[1] J. Burrows, S. Kamo, K. Koide, Science 2021, 374, 741-746 and cited literature.
[2] A. E. Goetz and Coll., Org. Process Res. Dev. 2023 (https://doi.org/10.1021/acs.oprd.3c00141)
