General procedure for the synthesis of (3aR,4S,7R,7aS)-rel-(3aR,4S,7R,7aS)-rel-hexahydro-1H-4,7-methanoisoindoline-1,3(2H)-dione from rel-(3aR,4S,7R,7aS)-3a,4,7,7a-tetrahydro-1H-4,7-methanoiisoindoline-1,3(2H)-dione: In an autoclave, 3.8 kg palladium carbon (10% w/w, 50% H2O) and the raw material rel-(3aR,4S,7R,7aS)-3a,4,7,7a-tetrahydro-1H-4,7-methylene-bridged isoindoline-1,3(2H)-dione (68.8 kg, 421.3 mol) were suspended in methanol (1000 L). Subsequently, the autoclave was sealed and the air in the autoclave was replaced with nitrogen, and then hydrogen was introduced to a pressure of 8 atm. The reaction process was monitored by hydrogen consumption and gas chromatography (GC). Upon completion of the reaction, the reaction solution was concentrated to a smaller volume and water (200 L) was slowly added over a period of about 30 min. The resulting suspension was cooled and a white solid was separated by centrifugation and washed with 50 L of water to give the final product (3aR,4S,7R,7aS)-rel-hexahydro-1H-4,7-bridged methylidene isoindole-1,3(2H)-dione (dry weight 63.6 kg, yield 91.4%, GC purity 99.99%).
