| 83% |
|
A solution of copper(II) bromide (3.6 g, 16.11 mmol) and n-amyl nitrite (1.07 mL, 8.06 mmol) in acetonitrile (22 mL) was heated to 60C, and a solution of ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate (1.0 g, 5.37 mmol) in acetonitrile (30 mL) was added dropwise thereto. The mixture was stirred for 4 hr at same temperature. The reaction mixture was allowed to cool to room temperature, and added into ice-cooled 1N aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate= 95:5→85:15) to give the title compound (1.1 g, 83%). 1H-NMR (CDCl3) δ : 1.37 (3 H, t, J = 7.1 Hz), 2.72 (3 H, s), 4.33 (2 H, q, J = 7.1 Hz). |
| 76% |
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0℃; for 4h; |
To a stirred solution of Intermediate 6 (0.53 g, 2.85 mmol) in MeCN (6 mL) at00C was added CuBr2 (0.70 g, 3.13 mmol) followed by dropwise addition of tert-buty nitrite (0.44 mL, 3.70 mmol). After stirring at 00C for 4 h, the reaction mixture was concentrated in vacuo to give a black oil. Purification by column chromatography (SiO2, 0-50% EtOAc/hexanes) gave the title compound (0.54 g, 76%) as a yellow solid. 6H (CDCl3) 4.33 (2H, q, J 7.0 Hz), 2.71 (3H, s), 1.36 (3H, t, J 7.2 Hz). MS (ES+) 252.0 (M+H)+. |
| 62% |
With potassium bromide; copper(I) bromide; sodium nitrite; In water; at 60℃; for 1h; |
Compound 3 (1 mmol) in HBr (3 mL) was added to cold aqueous solution of CuBr (1 mmol) and KBr(0.2 mmol) followed by dropwise addition of preliminary cooled aqueous solution of NaNO2(10 mL) for 1 h. The reaction mixture was stirred at 60C for 2 h. The reaction progress was monitored byTLC until the starting material completely disappeared.The reaction mixture was diluted with water,the obtained precipitate was filtered off to give ethyl 2-bromo-4-methylthiazole-5-carboxylate 4 as off-whitesolid in 62% yield. 1H NMR spectrum (CDCl3), δ,ppm: 4.28 q (2H), 2.81 s (3H), 1.33 t (3H). Massspectrum (ESI-MS): m/z 251 [M + H]+. |
| 59% |
With copper(I) bromide; isopentyl nitrite; In acetonitrile; at 80℃; for 4h; |
To a suspension of ethyl 2-amino-4-methylthiazole-5-carboxylate (1 g, 5.36 mmol, 1 eq) and CuBr2 (1.19 g, 5.36 mol, 1 eq) in acetonitrile (25 mL) was added isoamyl nitrite (2.16 mL, 16.08 mmol, 3 eq) dropwise at 25 C, and the reaction mixture was stirred at 80C for 4 h. The resulting reaction mixture was gradually cooled to 25 C and concentrated under reduced pressure to remove excess isoamyl nitrite and acetonitrile. The residue obtained was partitioned between water (250 mL) and ethyl acetate (250 mL), and the organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure to obtain the crude compound as a brownish solid. The crude product obtained was purified by silica gel (23 0-400) column chromatography (10% ethyl acetate in hexane) to obtain ethyl 2-bromo-4-methylthiazole- 5-carboxylate (800 mg, 59%) as a yellow solid. |
|
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 60℃; for 1h; |
Preparation of ethyl 2-bromo-4-methyithiazole-5-carboxylate (compound B: L=bromo: R=ethyl) To a solution of CuBr2 (75 gms/0.335 moles) in 750 ml acetonitrile was added t-butyl nitrite (28.6 gms/0.277 moles). The resultant mixture was heated to 60C and ethyl 2- amino-4-methylthiazole-5-carboxylate (35.0 gms/0.188moles) was further added in lots. The reaction mass was stirred for 1 hour at 60C. After completion of reaction, the reaction mass was cooled to 25C and about 150 ml water was added. The reaction mass was neutralized using 2N NaOH and extracted in ethyl acetate (300 ml). The organic layer was washed with water until a neutral pH. The separated organic layer was treated with charcoal. After drying the organic layer over anhydrous sodium sulphate, a clear filtrate was distilled off and 17.1 gms of the titled compound was obtained after drying at 40-45C as an off-white colored solid. Efficiency: 36% |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
