1-Hydroxybenzotriazole → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 100 L round-bottomed-flask equipped with a mechanical stirrer, thermocouple and nitrogen inlet was charged with DMF (51 L), N,O-dimethylhydroxyamine hydrochloride (2.62 Kg, 26.55 mol), HOBT (1.2 Kg, 8.85 mol), and N-Boc isonipecotic acid (4.10 Kg, 17.70 mol). The mixture warmed to 18 ° C. as the diisopropylethylamine (4.60 Kg, 6.2 L, 35.41 mol) was added over 15 min. The EDC.HCl (5.09 Kg, 26.55 mol) was added in three portions over 3 h maintaining an internal temperature of 18° C. with gentle cooling. The reaction mixture was held at 18° C. for 12 h. HPLC analysis shows no remaining 1. The reaction mixture was pumped into an extractor containing 74 L of water at 5° C. The resulting solution (39.3 g/L of 2) was extracted with ethyl acetate (4×37 L).

Provenance & Evidence