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 supply at RT, is added triethylamine (29.7 mL, 214 mmol) followed by DMSO (24 mL), giving an almost homogenous solution. The mixture is cooled to 0° C. (ice/salt bath), and to this is 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 is stirred at 0-5° C. over a 1 h period then allowed to warm to RT over 2 h. The mixture is cooled to 0° C. in an ice bath and is quenched by the addition of 1M HCl (aq) (40 mL) dropwise over 30 min. The mixture is then diluted with water (60 mL) and DCM (150 mL). 2 M HCl is added to give pH˜1-2. The organic phase is separated, washed again with 2 M HCl (100 mL), followed by sat. NaHCO3 (100 mL). The organic layer is diluted with EtOAc (800 mL) and is vigourously stirred at RT. The mixture is then filtered removing some insoluble material in the process. The now clear two phase mixture is separated, the organic (EtOAc) layer is dried over over MgSO4 and is filtered and concentrated to give an off white solid. The crude solid is suspended in diethylether (500 mL) and is triturated, removing some brown/yellow colour. The solid is allowed to settle, and the liquors are decanted off. The solid is then triturated in iso-hexane (300 mL), using the same procedure twice, then the solid is transferred to a small flask in iso-hexane slurry and is dried in vacuo to give an off-white solid; [MH+ 334]

Provenance & Evidence