Toluene → tert-Butyl 2,9-diazaspiro(5.5)undecane-9-carboxylate

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Reaction Steps

Charge 435 g of toluene then 302.1 g of sodium bis(2-methoxyethoxy)aluminum hydride to R1. Cool the mixture to −5° C.˜5° C. Charge 652.5 g of toluene and 50 g of tert-butyl 4-(3-chloropropyl)-4-cyano-piperidine-1-carboxylate into R2 and stir the mixture until clear. Add the solution of tert-butyl 4-(3-chloropropyl)-4-cyano-piperidine-1-carboxylate in R2 drop-wise to R1, control the temperature below 5° C. Stir the mixture in R1 for 0.5 hour at −5° C.˜5° C. then warm the mixture to 15˜20° C. and stir for 1˜3 hours. Charge 25 g of sodium carbonate to R2 then add 1500 g of water and cool the mixture to 0˜10° C. Add the mixture in R1 drop-wise to R2, controlling the temperature below 10° C. Warm the mixture to 20˜40° C. and stir for 10-20 mins then allow to stand for 40-60 mins Separate the aqueous layer and wash the organic layer with 2×250 g water then 297.5 g of 25% aqueous sodium chloride solution. Concentrate the organic layer to 100 g total weight below 50° C. and then add 273.0 g of acetonitrile. Concentrate the organic layer to 250 g total weight below 50° C. of title compound, tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate, which is stored as a solution: mass spectrum (m/z): 255 (M+H).

Provenance & Evidence