Acetic Acid → 4-[2-(4-Bromo-2-methyl-phenylamino)-ethyl]-tetrahydro-pyran-4-carboxylic acid methyl ester

Beteiligte Stoffe

Reaktionsschritte

2-Methyl-4-bromo-aniline (1.20 g, 6.45 mmol) was dissolved in DCE (30 mL); to this solution was transferred a solution of 4-(2-oxo-ethyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (1.20 g, 6.44 mmol in DCE (30 mL). The flask was submerged in a water bath at rt. To this clear solution was then added acetic acid (1.2 g, 20 mmol, 3.1 equiv), followed by addition of powder NaBH(OAc)3 (24.1 g, 19.3 mmol, 3 equiv. in 2 portions under N2 at r.t. The yellowish milky suspension was stirred at r.t. overnight. LC/MS showed m/z 356/358 at t=3.955 min. along with small amount of aniline sm at 2.078 (186/188). There was no di-alkylated product detected (MW 526.47). TLC (5% of MeOH in DCM) showed no SM aldehyde, but aniline. The reaction was diluted with DCM (30 mL), cooled to ice-water bath, and quenched with an aqueous solution of 10 mL of conc. NH4OH (7.45M) in 30 mL of water. (2 M of NH4OH). The two layers were separated, and the aqueous layer was extracted with DCM (20 mL×2). The combined DCM extracts were washed with sodium bicarbonate (20 mL), and brine (20 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The product was purified on a 40-g silica gel column (0-5% B: 0-4 min; 5-15% B 4-13 min; 20% B: 13-25 min (B is 10% MeOH in DCM) to get 2.00 g (87%) of the title compound as an oil.

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