30830-27-4

917887-34-4

30830-27-4

The general procedure for the synthesis of 3-(benzyloxy)-1-cyclobutanone from the compound (CAS: 917887-34-4) was as follows: 26.5 L of diethyl ether was added to a 30-35 L reactor and the reactor was water cooled at the beginning of the addition. 1.064 kg of compound (VII) was added to the reactor. 0.932 L of perchloric acid (60%) was pre-diluted with 0.664 L of water and added slowly to the reactor over 20-30 minutes at 10°C. After addition of the acid, cooling was stopped and the reaction was stirred vigorously overnight at about 20°C. The reaction was quenched by the addition of 900 g of NaHCO3 dissolved in 8 L of water until the pH was about 7. The aqueous phase was discarded and the reaction mixture was washed with an additional 7 L of water. The ether was removed under vacuum, 2 L of toluene was added, and the crude mixture was azeotropically dried. The crude product was diluted to about 2 L with toluene and loaded onto a silica gel pad. The pad was wet packed and pre-eluted with toluene. For the separation of 1.5 kg batches, a silica gel pad with a diameter of 40 cm and a height of 22 cm was used. After the crude product was applied to the pad, it was eluted with eluent in the following order: 3 x 10 L toluene; 9 x 10 L toluene: ethyl acetate (95:5). The product grades were collected and the solvent was evaporated under vacuum. High vacuum was required to remove the last 5% of toluene. Final isolation gave 533 g of product (yield = 77%).GC analysis showed 95% product purity. The 1H NMR (500 MHz, CDCl3) data for compound (VIII) were as follows: δH 7.40-7.29 (m, 5H), 4.53 (s, 2H), 4.38 (tt, J = 6.6, 4.7Hz, 1H), 3.3-3.1 (m, 4H).