N-[4-(AMinocarbonyl)-3-fluorophenyl]-2-Methylalanine synthesis

Yield:-

Reaction Conditions:

with potassium carbonate;copper(l) iodide;2-acetylcyclohexanone;triethylamine in water;N,N-dimethyl-formamide at 95 - 100; for 48 h;

Steps:

6b

4-Bromo-2-fluorobenzamide (0.5 g, 2.29 mmol), 2 aminoisobutyric acid (0.354 g,3.54 mmol), CuI (87 mg, 0.458 mmol), and K₂CO₃ (0.790 g, 5.72 mmol) were mixed in DMF (5 mL). H₂O (0.5 mL) and TEA (11 mg, 0.1 mmol) were added followed by 2-acetyl cyclohexanone (60 mg, 0.428 mmol). The reaction mixture was heated to 95-100 °C for 48 h. The reaction mixture was diluted with H₂O (20 mL) and the aqueous layer was washed with ethyl acetate (20 mL). The aqueous layer was acidified with IM citric acid to pH 4 and the product was extracted with ethyl acetate (20 mL x 3). The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to obtain the product. ¹H NMR (DMSO, Freebase): δ (ppm) 7.55-7.45 (t, IH), 7.20 (bs, IH), 7.05 (bs, IH), 6.80 (bs, IH), 6.35-6.30 (d, IH), 6.18-6.10 (d, IH), 1.42 (s, 6H).

References:

WO2010/99238,2010,A1 Location in patent:Page/Page column 33