Ethanolamine → 3-cyano-N-(2-hydroxyethyl)-4-isopropoxybenzamide

Temperature

50 °C

To a stirring suspension of 3-cyano-4-isopropoxybenzoic acid (1.0 g, 4.8 mmol) in DCM (20 mL) was added oxalyl chloride (3.7 g, 29.2 mmol) followed by two drops DMF. The reaction mixture was stirred at 50° C. for 2 h. The mixture was concentrated and the residue re-dissolved in DCM (10 mL). Ethanolamine (0.6 g, 9.7 mmol) and TEA (1.45 g, 14.4 mmol) were added and the reaction mixture was stirred overnight at room temperature. The resulting solid was filtered, washed with water, and dried to afford 1.0 g (83%) of 3-cyano-N-(2-hydroxyethyl)-4-isopropoxybenzamide which was used in the next step without purification. LCMS-ESI (m/z) calculated for C13H16N2O3: 248.3; found 249.0 [M+H]+, tR=2.41 min. 1H NMR (400 MHz, CDCl3) δ 8.02-7.79 (m, 2H), 6.97-6.87 (m, 1H), 6.71 (s, 1H), 4.65 (dt, J=12.1, 6.1 Hz, 1H), 3.82-3.70 (m, 2H), 3.56 (dd, J=10.2, 5.5 Hz, 2H), 1.96 (d, J=10.0 Hz, 1H), 1.40-1.29 (m, 6H).

1. concentrationThe mixture was concentrated
2. dissolutionthe residue re-dissolved in DCM (10 mL)
3. stirringthe reaction mixture was stirred overnight at room temperature
4. filtrationThe resulting solid was filtered
5. washwashed with water
6. customdried

ORD record

ord-70a3a30160e744aa9e8aa1d33c11b069

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394264B2