Dimethylamine → (S)-2-(4-Aminophenyl)-2-(isopropyl(methyl)amino)-N,N-dimethylacetamide

Participants

Reaction Conditions

Reaction Steps

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 22 (116 mg, 0.36 mmol), 1-hydroxy-7-azabenzotriazole (50 mg, 0.37 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (208 mg, 1.08 mmol) and DMF (2 mL), and the mixture was cooled to 0° C. A 2M solution of dimethylamine in THF (0.3 mL, 0.6 mmol) was added, and the reaction was allowed to warm slowly to room temperature overnight. A solution of potassium carbonate (2.00 g) in water (10 mL) was added, and the mixture was extracted with hexanes (3×30 mL). The hexanes extracts were combined, dried over sodium sulfate, filtered, and evaporated to dryness. The resulting crude product was mixed with methylene chloride (1 mL) and 4M solution of hydrogen chloride in dioxane (10 mL). The resulting emulsion was vigorously stirred for 1 h at room temperature. After this time, the solvents were evaporated under reduced pressure, and the resulting residue was treated with water (2 mL) followed by potassium carbonate (1.0 g), and then extracted with MtBE (10 mL). The extract was evaporated and the residue was purified by flash chromatography on silica gel to afford a 58% yield (53 mg) of 23 as a light yellow oil: 1H NMR (300 MHz, CDCl3/CD3OD) δ 7.20 (d, 2H, J=8.5 Hz), 6.69 (d, 2H, J=8.5 Hz), 4.56 (s, 1H), 3.02 (s, 3H), 2.97 (m, 1H), 2.91 (s, 3H), 2.11 (s, 3H), 1.03 (d, 3H, J=6.7 Hz), 1.00 (d, 3H, J=6.6 Hz).

Provenance & Evidence