Hydrogen Peroxide → ditert-butyl(1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

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Reaction Steps

Add 1M lithium tri(sec-butyl)borohydride in tetrahydrofuran (2.67 L, 2.67 mol) dropwise to a solution of di-tert-butyl(1S,2S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate (1000 g, 2.43 mol) in dry tetrahydrofuran (10 L) at 0° C. under nitrogen. After 2 hours at 0° C., 2M Na2CO3 in water (850 g, 8.02 mol) is added at 0° C. over 2 hours followed by 35% aqueous hydrogen peroxide (740 mL, 8.99 mol) in water (3.3 L). After 40 minutes, the mixture is warmed to ambient temperature whereupon the organic phase is separated. The organic phase is diluted with methyl tert-butyl ether (3.5 L) and the layers are separated again. The aqueous phase is extracted with methyl tert-butyl ether (3.5 L). All the combined organic phases are washed successively with 1M aqueous Na2SO3 (2.67 L), water (2.67 L), and brine (2.67 L), dried over sodium sulfate, filtered and concentrated to a volume of 3 L. The precipitated solid is filtered and washed with heptane (1.3 L) to obtain the title compound (864.76 g). The mother liquors are concentrated to dryness and the residue is triturated with heptane (500 mL) and filtered to obtain additional title compound (130.64 g, total 995.4 g, yield 99%). MS (m/z): 436 (M+23).

Provenance & Evidence