Phosphorus oxychloride → 4-Methylthiazole-2-carboxylic acid (2-acetyl-5-methoxyphenyl)amide

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2.59 g (15.7 mmol) of 2-amino-4-methoxybenzophenone (product of step D) and 2.68 g (15.7 mmol) of 4-isopropylthiazole-2-carboxylic acid (product of step 77c) in 75 mL of pyridine cooled to −30° C., was added 1.93 mL (23.5 mmol) of POCl3 slowly dropwise over 5 min. The mixture was stirred 3 h, warmed to room temperature and was stirred overnite. The reaction mixture was poured into ice water, and extracted several times with EtOAc. The combined EtOAc extracts were dried (MgSO4), concentrated and chromatographed over SiO2 (eluted with 0% to 15% MeOH/EtOAc) to afford 2.57 g (51%) of 4-Methylthiazole-2-carboxylic acid (2-acetyl-5-methoxyphenyl)amide as a yellow solid: 1H NMR (CDCl3) δ ppm 1.41 (d, J=6.7 Hz, 6H), 2.64 (s, 3H), 3.24 (m, 1H), 3.91 (s, 3H), 6.67 (dd, J=9, 2.5 Hz, 1H), 7.18 (s, 1H), 7.86 (d, J=9 Hz, 1H), 8.56 (d, J=2.5 Hz, 1H), 13.48 (s, 1H).

Provenance & Evidence