反应详情

4-Hydroxymethyl-2-(2-methylphenyl)benzoic acid (69 g, 285 mmol), prepared as in example 1075E, L-methionine methyl ester.HCl (68.3 g, 342 mmol), 1-hydroxybenzotriazole (46.2 g, 342 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (65.6 g, 342 mmol) were dissolved at ambient temperature in DMF (700 mL). To this solution was added triethylamine (47.7 mL, 342 mmol) and the resulting thick slurry was stirred overnight at ambient temperature. The reaction was diluted with EtOAc (700 mL) and washed with water (2×1L), saturated NaHCO3 (2×500 mL), 1N H3PO4 (2×500 mL), and brine. Organic layer dried with Na2SO4, filtered, and concentrated in vacuo to produce a pale yellow solid (110 g, 100% crude yield). 1H(300 MHz, CDCl3) δ 7.93 (1H, m), 7.44 (1H, dd, J=8, 2 Hz), 7.40-7.20 (4H, m), 7.19 (1H, bs), 5.92 (1H, m), 4.78 (2H, s), 4.63 (1H, m), 3.66 (3H, s), 2.20-2.00 (8H, m), 1.87 (1H, m), 1.75 (1H, m), 1.60 (1H, m). m/e (ESI) 386 (MH−).

1. washwashed with water (2×1L), saturated NaHCO3 (2×500 mL), 1N H3PO4 (2×500 mL), and brine
2. dry with materialOrganic layer dried with Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customto produce a pale yellow solid (110 g, 100% crude yield)