5-Fluoro-2-iodobenzoic acid synthesis
- Product Name:5-Fluoro-2-iodobenzoic acid
- CAS Number:52548-63-7
- Molecular formula:C7H4FIO2
- Molecular Weight:266.01
446-08-2
52548-63-7
Step 1: 2-Amino-5-fluorobenzoic acid (25 g, 0.162 mol) was dissolved in 2N HCl solution (350 mL) and cooled to 0-5°C. At this temperature, a solution of sodium nitrite (11.2 g, 0.16 mol) in water (150 mL) was slowly added dropwise. After the dropwise addition was completed, the reaction mixture was continued to be stirred at 0-5°C for 90 min. Subsequently, the resulting diazonium salt solution was added dropwise to a solution of potassium iodide (53 g, 0.32 mol) and cuprous(I) iodide (15.2 g, 0.081 mol) in water (150 mL) that had been pre-cooled to about 5 °C. After completion of the dropwise addition, the reaction mixture was transferred to room temperature and stirred for 18 hours. The completion of the reaction was monitored by TLC (unfolding agent: EtOAc). At the end of the reaction, the mixture was filtered and the solid product was collected. The solid residue was diluted with methyl tert-butyl ether (MTBE, 500 mL), refluxed for 20 min and filtered. The filtrate was concentrated to give 5-fluoro-2-iodobenzoic acid (30 g, 75% yield) as a yellow solid. The product was characterized by 1H NMR (400 MHz, methanol-d4): δ 8.04-8.00 (m, 1H), 7.59-7.56 (m, 1H), 7.08-7.03 (m, 1H).
446-08-2
398 suppliers
$14.00/5g
52548-63-7
161 suppliers
$8.00/250mg
Yield:52548-63-7 75%
Reaction Conditions:
Stage #1: 2-amino-5-fluorobenzoic acidwith hydrogenchloride;sodium nitrite in water at 0 - 5;
Stage #2: with copper(l) iodide;potassium iodide in water at 5 - 20;
Steps:
Step 1 : To a solution of compound 8 (25 g, 0.162 mol) in 2 N HCI solution (350 mL) was added a solution of sodium nitrite (1 1.2 g, 0.16 mol) in H20 (150 mL) drop-wise while maintaining the temperature between 0 - 5 °C. After the addition was completed, the mixture was stirred at 0-5 °C for 90 minutes. Then, the mixture was added to a solution of potassium iodide (53 g, 0.32 mol) and copper (I) iodide (15.2 g, 0.081 mol) in H20 (150 mL) drop-wise with the temperature maintained at ~5 °C. After addition was completed, the mixture was stirred at room temperature for 18 hours after which TLC (EtOAc) indicated that the reaction was complete. The mixture was filtered and the cake dried. The residue was diluted with MTBE (500 mL), refluxed for 20 minutes, and filtered. The filtrate was concentrated to afford compound 9 as a yellow solid (30 g, 75% yield). 1 H NMR (400 MHz, Methanol-d4) δ 8.04 - 8.00 (m, 1 H), 7.59 - 7.56 (m, 1 H), 7.08 - 7.03 (m, 1 H).
References:
WO2013/132376,2013,A1 Location in patent:Page/Page column 151
326-65-8
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$60.00/50mg
52548-63-7
161 suppliers
$8.00/250mg
49579-56-8
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$19.00/250mg
52548-63-7
161 suppliers
$8.00/250mg