Triethylamine → HCID 178520978, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of trans-2-chloro-N-(4-hydroxymethyl-cyclohexyl)-5-trifluoromethyl-benzamide (step 2) (24 g, 71.5 mmol) in DCM (72 ml) under N2 at RT, was added triethylamine (29.7 ml, 214 mmol) followed by DMSO (24 ml), giving an almost homogenous solution. The mixture was cooled to 0° C. (ice/salt bath), and to this was added dropwise a solution/suspension of sulfur trioxide-pyridine complex (34.1 g, 214 mmol) in DMSO (30 ml): DCM (20 ml) over a period of ˜90 min. The mixture was stirred at 0-5° C. over a 1 h period then allowed to warm to RT over 2 h. The mixture was cooled to 0° C. in an ice bath and was quenched by the addition of 1 M HCl (aq) (40 ml) dropwise over 30 min. The mixture was then diluted with water (60 ml) and DCM (150 ml). 2 M HCl was added to give pH ˜1-2. The organic phase was separated, washed again with 2 M HCl (100 ml), followed by sat. NaHCO3 (100 ml). The organic layer was diluted with EtOAc (800 ml) and was vigourously stirred at RT. The mixture was then filtered removing some insoluble material in the process. The now clear two phase mixture was separated, the organic (EtOAc) layer was dried (MgSO4), filtered and concentrated to give an off white solid. The crude solid was suspended in diethylether (500 ml) and triturated, removing some brown/yellow colour. The solid was allowed to settle, and the liquors were decanted off. The solid was then triturated in iso-hexane (300 ml), using the same procedure twice, then the solid was transferred to a small flask in iso-hexane slurry and was dried in vacuo to give an off-white solid; [M+H]+334

Provenance & Evidence