Dimethylamine → HCID 45807263, compound

Participants

Reaction Steps

1-(4-Bromophenyl)cyclopropanecarboxylic acid (247, 1.00 g, 4.15 mmol) was dissolved in 10 mL DMF and 90 mL dioxane. To it were added dimethylamine (2M in THF, 10.4 mL, 20.7 mmol) and then PyBOP (4.32 g, 8.30 mmol). The mixture was stirred at RT for 2 hours, concentrated in vacuo, diluted with 100 mL EtOAc, washed with water ×3, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 3% MeOH in DCM to isolate 1-(4-bromophenyl)-N,N-dimethylcyclopropanecarboxamide (248) in quantitative yield. It was dissolved in 100 mL dioxane. To the solution were added tert-butyl carbamate (2.91 g, 24.9 mmol), Pd2(dba)3 (760 mg, 0.83 mmol), XantPhos (1.44 g, 2.49 mmol), fine-powder cesium carbonate (8.12 g, 24.9 mmol). The mixture was degassed using N2 stream for 5 min, and stirred under N2 atmosphere at 115° C. for 2 days. It was cooled to RT, concentrated in vacuo, diluted with 200 mL EtOAc, washed with water ×3, dried, concentrated, and subjected to silica flash column to isolate tert-butyl 4-(1-(dimethylcarbamoyl)cyclopropyl)phenylcarbamate (249, 600 mg). It was treated with 20 mL commercial 4N HCl in dioxane at RT for 1.5 hour. The mixture was concentrated in vacuo to dryness to give 1-(4-aminophenyl)-N,N-dimethylcyclopropanecarboxamide (250) as HCl salt.

Provenance & Evidence