ethyl 4-phenylthiazole-5-carboxylate synthesis

Yield:99822-80-7 30%

Reaction Conditions:

Stage #1: ethyl 4-phenyl-2-aminothiazole-5-carboxylatewith sulfuric acid;sodium nitrite in water at 0;
Stage #2: with hypophosphorous acid in water at 0 - 5; for 1 h;

Steps:

17 4.1.17. Ethyl 4-phenyl-1,3-thiazole-5-carboxylate (22)

4.1.17
Ethyl 4-phenyl-1,3-thiazole-5-carboxylate (22)
To a mixture of ethyl 2-amino-4-phenyl-1,3-thiazole-5-carboxylate
¹⁴
(21 6.00 g, 24.2 mmol) and 50% aqueous H₂SO₄ (80 mL), NaNO₂ (2.0 g, 29.0 mmol) in H₂O (10 mL) was added dropwise below 0 °C. Subsequently, 50% aqueous H₃PO₂ (35.1 g, 266 mmol) was added to the mixture below 0 °C.
The mixture was stirred for 1 h below 5 °C and then diluted with H₂O (100 mL) and adjusted to pH 9-10 with 10 M NaOH.
The mixture was extracted with AcOEt, and the organic layer was dried and concentrated in vacuo.
The residue was chromatographed on silica gel with elution using hexane/AcOEt (97:3 to 85:15) to produce the desired compound 22 (1.68 g, 30%) as an orange oil. ¹H NMR (DMSO-d₆) δ 1.21 (3H, t, J = 7.2 Hz), 4.23 (2H, q, J = 7.2 Hz), 7.43-7.47 (3H, m), 7.70-7.75 (2H, m), 9.33 (1H, s); FAB MS m/e [M+H]⁺ 234.

References:

Nagashima, Shinya;Matsushima, Yuji;Hamaguchi, Hisao;Nagata, Hiroshi;Kontani, Toru;Moritomo, Ayako;Koshika, Tadatsura;Takeuchi, Makoto [Bioorganic and Medicinal Chemistry,2014,vol. 22,# 13,p. 3478 - 3487]