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ChemicalBook CAS DataBase List 5-Bromothiazole
3034-55-7

5-Bromothiazole synthesis

4synthesis methods
5-Bromothiazole is a monobromothiazole, which can be prepared via treatment of 2,5-dibromothiazole with sodium ethoxide followed by hydrogenation over spongy nickel.
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Yield:-

Reaction Conditions:

Stage #1:5-bromo-2-aminothiazole with phosphoric acid;nitric acid;sodium nitrite in water at -5; for 1 h;
Stage #2: with hypophosphorous acid in water at 0 - 20;

Steps:


To a solution of 2-amino-5-bromothiazole (12.58g, 70mmol) in a mixture of phosphoric acid (106ml of an 86% solution in water), and cone, nitric acid (19.2ml) cooled at - 50C was added over 45 mins a solution of sodium nitrite (7.59g, 1 lOmmol) in water (26ml). 30 After the addition was complete the mixture was stirred at -50C for 15 mins, then hypophosphorous acid (38.8ml) added dropwise over 30 mins keeping the temperature below O0C. The mixture was stirred at O0C for 150 mins then allowed to warm to room temperature overnight. The mixture was poured into a solution of NaOH (85g) in water (400ml). 5N NaOH EPO solution added until the mixture reached neutrality, and the resulting mixture extracted with CH2Cl2 (3 x 200ml). Combined CH2Cl2 layers washed with sat. NaCl, dried over Na2SO4, filtered and evaporated. The residue was purified by MPLC on silica gel eluting with a gradient rising from 100% hexanes to 10% EtOAc in hexanes to give of the title compound. HNMR 5 (500 MHz, CDCl3) δ: 8.78 (s, IH), 7.83 (s, IH).

References:

MERCK & CO., INC. WO2008/57336, 2008, A2 Location in patent:Page/Page column 40-41

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