57280-22-5

Clear colorless to yellow liquid

4,4-Dimethyl-3,5,8-trioxabicyclo[5.1.0]octane is used in the CO2-mediated formation of chiral carbamates from meso-epoxides via polycarbonate intermediates and amine nucleophiles, which opens up a wide a wide range of CO2-based carbamate scaffolds with excellent yields and 99% enantiomeric excess.

4, 4-dimethyl-3,5, 8-trioxane [5,1,0] octane is a key intermediate in the preparation of gadobinol. As a meso epoxide, it could be used to obtain optically pure ABT derivatives through Ti(IV)/BINOL catalyzed asymmetric aminolysis[1].

1) 1810 kg of 4,7-dihydro-2,2-dimethyl-1,3-dioxepin (Compound A-3), 1730 kg of acetonitrile, 1480 kg of methanol, and 1920 kg of water were added to the reaction vessel, followed by 15.1 kg of disodium hydrogen phosphate; the reaction solution was stirred and heated. 2) 1990 kg of 27% hydrogen peroxide and 1086 kg of aqueous 1 M sodium hydroxide were added to the reactor, and the reaction temperature was controlled at 60-80°C; the pH was maintained at 7-9.5 during the reaction. 3) After the reaction was completed, the reaction solution was stirred to room temperature for 8 to 9 hours. 4) 2880 kg of saturated brine and 6335 kg of dichloromethane were sequentially added to the reactor, and the organic phase was separated after stirring. 5) Add 4010 kg of sodium sulfite solution to the organic phase, stir and dry the organic phase. 6) After drying, the organic phase was filtered and the solvent was removed by distillation at 40°C to obtain a crude product of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane (Compound A). (7) The crude compound A was subjected to decompression distillation to obtain the pure compound A (1820 kg, total yield: 85.2%), which was tested to be ≥99.6% pure.

[1] Bao H, et al. Insight into the Mechanism of the Asymmetric Ring-Opening Aminolysis of 4,4-Dimethyl-3,5,8-trioxabicyclo[5.1.0]octane Catalyzed by Titanium/BINOLate/Water System: Evidence for the Ti(BINOLate)2-Bearing Active Catalyst Entities and the Role of Water. Journal of the American Chemical Society, 2008; 130: 10116–10127.