Carbon Dioxide → (1S,4R)-(-)-4-(Boc-amino)-2-cyclopentene-1-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Di-tert-butyl dicarbonate (968 g) was added to a stirred solution of racemic 2-aza bicyclo[2.2.1]hept-5-ene-3-one (1)(440 g) in tetrahydrofuran (THF)(1800 ml). A catalytic amount of 4-dimethylaminopyridine (DMAP)(4.9 g) was added as a single bolus and the solution stirred at ca 25-30° C. until the evolution of carbon dioxide had ceased. A solution of sodium hydroxide (177.4 g) in water (4400 ml) was added to the thus formed 3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylic acid, 1,1-dimethylethyl ester (2) and the reaction heated to 40° C. for 15 hours. The reaction mixture was cooled and partitioned with toluene (3500 ml). The phases were separated and the aqueous layer extracted with more toluene (1700 ml). The aqueous layer was treated with activated charcoal (44 g) at ambient temperature, filtered and then acidified to pH3.6 with concentrated hydrochloric acid (400 ml). The precipitated product was filtered off, washed with water (400 ml) then dried in vacuo at 50° C. The yield of 4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-cyclopentene-1-carboxylic acid was 882 g, 96% of theory. Mp 125-28° C.

Provenance & Evidence