Aniline → HCID 51358155, compound

Participants

Reaction Conditions

Reaction Steps

A jacketed 30-L 3-neck bottom-valve cylindrical reactor equipped with overhead stirrer, reflux condenser, addition funnel, and N2 inlet was flushed with N2. Water (8.7 L) was charged followed by aniline (423 L, 4.9 mol). Stirring was initiated and the internal temperature set for 80° C. After the internal temperature reached 77° C., (R)-β-butyrolactone was charged over 1.5 h via addition funnel. The internal temperature was maintained between 80-81.7° C. during the course of addition. Once addition was completed, reaction was cooled to 20° C. over 1 h. K2CO3 (250 g, 1.8 mol, 0.75 equiv) was charged as a solid, and the aqueous pH was determined to be 10. The aqueous phase was extracted with MTBE (3×2 L), and the extracts were discarded. After adjusting the pH of the aqueous phase to 5 with 6 N HCl (225 mL), it was extracted with EtOAc (3×2 L). After each extraction, the pH was checked and was readjusted to 5 with 6 N HCl as necessary. The combined EtOAc extracts were washed with saturated brine (2 L), dried with MgSO4, and concentrated via rotary evaporation to produce a pink oil. Recovery: 300 g (72%). Enantiomeric excess was determined by chiral HPLC to be 94%.

Provenance & Evidence