Cuprous bromide synthesis

Yield:-

Reaction Conditions:

Stage #1: copper(II) sulfate;sodium bromide in water;
Stage #2: with sodium sulfite in water;
Stage #3: with hydrogen bromide in hexane;

Steps:

28

Example 2828.1 28.2[0329] Methyl 4-bromo-3-(trifluoromethoxy)benzoate (28.2). To a solution of 4-amino-3-(trifluoromethoxy)benzoic acid (2.00 g, 9.10 mmol) in MeOH (25.0 mL), was slowly added HCl (1.0 mL, 1.0 M in ether) at room temperature. The resulting reaction mixture was stirred at room temperature overnight. Benzene (20 mL) was added, and the reaction was heated at reflux with a Dean-Stark trap to remove the half volume of the solvent. The rest of the solvent was then evaporated to give the product. MS (ESI) m/e = 235.9 [M+l]⁺, Calc'd for CgHeF₃NOs, 235.1. The crude product was used in the next step without further purification. To an ice-cooled suspension of methyl 4-amino-3- (trifluoromethoxy)benzoate hydrogen chloride salt (8.60 g, 31.70 mmol) in 17.1 mL of water and concentrated HBr (48 %, 17.1 mL), was slowly added a prepared 2.5 M solution of sodium nitrite (2.20 g in 12.7 mL) at 0⁰C. The reaction mixture was stirred at 0 ⁰C for 10 minutes. Meanwhile, a solution OfCuSO₄ (6.68 g) in 35 mL of water was heated and sodium bromide (6.52 g) was added. The solution became a green color, and a solution OfNa₂SOs (2.80 g) in water (10 mL) was then added to it. The solution was cooled at 0 ⁰C and washed with water (25 x 3 mL). The water was then decanted off. Concentrated HBr (16.7 mL) was added, and the solution became a purple color. The solution of CuBr was slowly added to the diazonium salt (prepared above) at 0⁰C. After addition, the ice-bath was removed, and an oil-bath was placed under the reaction vessel. The reaction mixture was then heated to 60⁰C for 15 minutes, at 80 ⁰C for 15 minutes, and then at 100⁰C for 20 minutes. The reaction mixture was next cooled to room temperature and made basic with Na₂CO₃ to a pH 8. The aqueous solution was extracted with EtOAc (100 x 2 mL). The organic layer was washed with brine (25 mL) and dried with MgSO₄. The solvent was removed to give the crude product 28.2. ¹H NMR (CDCl₃) δ 3.96 (s, 3H), 7.75 (d, J= 8.4 Hz₅ 1 H), 7.86 (d, J= 8.4 Hz, 1 H), 7.98 (s, IH).

References:

WO2008/30520,2008,A1 Location in patent:Page/Page column 136