Citric Acid → HCID 23653609, compound

Participants

Reaction Steps

Under a nitrogen atmosphere, solid (E)-3-[1-(8-chloro-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-phenylamine (198 g, 545 mmol), pyridine (67.0 mL, 828 mmol) and dichloromethane (1.6 L) are charged to a 5 liter 4 neck round bottom flask equipped with a mechanical stirrer and thermocouple. To the dark green reaction mixture, a solution of methanesulfonyl chloride (51.0 mL, 658 mmol) in dichloromethane (400 mL) is added dropwise over 20 min from an addition funnel. An exotherm of 6.9° C. is observed over the course of the addition. Upon completion of addition the reaction is stirred for 16 h at ambient temperature. The mixture is charged to a 22 L bottom outlet flask containing 10% citric acid solution (2 L). The mixture is stirred for 15 min and the layers separated upon standing. The organic layer is washed with a 15% NaCl solution. The organic layer is charged to a 5 L 4 neck flask, equipped with a mechanical stirrer under a nitrogen atmosphere. The deep red solution is treated with DARCO® activated charcoal (200 g), Na2SO4 (200 g) and TMT (trithiocyanuric acid trisodium salt hydrate) (50 g). The mixture is stirred for 18 h at ambient temperature and then filtered over a 2 in (about 5 cm) pad of diatomaceous earth (Hy-flo Supercel®). The filtrate is concentrated in vacuo yielding a hard white foam. Isopropyl alcohol (1 L, 5 volumes) is added to the foam and the slurry is stirred at 40° C. for one hour. The thick mixture is cooled to ambient temperature. The solids are vacuum filtered over a polypropylene pad in a buchner funnel The material is dried at 70° C. for 16 h under house vacuum yielding 171.85 g (71.4%) of white crystalline product. LC-ES/MS m/e 441.2 [M+H]+, 439.1 [M−H]−. Anal. Calcd for C23H21N2ClO3S: C, 62.65; H, 4.80; N, 6.35. Found: C, 62.81; H, 4.82; N, 6.20.

Provenance & Evidence