Cesium carbonate → N-(4-ethoxyphenyl)-2-hydroxy-2-methylpropionamide

To a solution of 4-ethoxyphenol (511 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150° C. for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2×50 mL), dried (Na2SO4), and concentrated to about 2 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluting with 3:7 EtOAc/hexane to obtain N-(4-ethoxyphenyl) -2-hydroxy-2-methylpropionamide as an off-white solid (536 mg, 2.40 mmol, 64.8% yield).: mp 146-148° C. 1H NMR (400 MHz, CDCl3) δ 8.59 (br s, 1H, N--H), 7.45 (dd, 2H, Ar--H, J=9.0, 2.2 Hz), 6.84 (dd, 2H, Ar--H, J=9.0, 2.2 Hz), 4.00 (q, 2H, CH2 -CH3, J=7.1 Hz), 2.73 (br s, 1H, O--H), 1.53 (s, 6H, C(CH3)2), 1.39 (t, 3H, CH2 -CH3, J=7.1 Hz); 13C NMR (75 MHz, CDCl3) δ 174.0, 155.7, 130.6, 74.0, 63.7, 27.9, 14.8; IR (KBr pellet) 1604, 1647 (amide C=O stretches), 3256 (NH stretch), 3281 (OH stretch); MS (CI/CH4) 224;

1. stirringthe resulting mixture was stirred
2. temperatureat reflux for 16 h
3. stirringThe resulting mixture was stirred at 150° C. for 72 h
4. temperatureThe reaction was cooled to room temp.
5. custompartitioned between water (50 mL) and EtOAc (100 mL)
6. extractionThe aqueous layer was extracted with EtOAc (100 mL)
7. washthe combined organics washed with water (2×50 mL)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated to about 2 g of material
10. customThe brown oil was chromatographed on silica (200 mL, 4 cm diam. column)
11. washeluting with 3:7 EtOAc/hexane

ORD 기록

ord-db316e15687244b6a0e922cf20ea69a5

출처 데이터셋

uspto-grants-1998_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05817874