A common heterocyclic compound, 437-82-1, name is 2,6-Difluoroanisole, molecular formula is C7H6F2O, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 437-82-1.
Step 1. Preparation of 3,5-difluoro-4-methoxyacetophenone To a stirred suspension of AlCl3 (24.05 g, 180.40 mmol) in chloroform (300 mL, dried by passage through alumina) at 4 C. (ice bath) under nitrogen was added acetyl chloride (11.0 mL, 152.65 mmol) over 20 minutes. This chilled suspension was stirred at 0 C. for 30 minutes and 2,6-difluoro anisole was added dropwise over 30 minutes. The resulting suspension was warmed to room temperature and stirred overnight. The reaction was quenched by slowly pouring it into a rapidly stirred ice/water mixture. The water layer was extracted with methylene chloride (2*50 mL) and the organic phases were combined and concentrated in vacuo yielding a clear mobile oil. In a 50 mL round bottomed flask was added the above clear oil, DMF (25 mL), K2 CO3 (15 g). Methyl iodide (6 mL) was added and the suspension stirred at 45 C. under nitrogen overnight. water (1 mL) was added and the mixture was heated for an additional 14 hours. The crude reaction mixture was cooled to room temperature, diluted with water (250 mL) and extracted with diethyl ether (3*100 mL). The ether phase was washed with sodium bicarbonate saturated solution, potassium bisulfate (0.1N solution), dried over MgSO4, filtered and concentrated in vacuo yielding a clear mobile liquid. This liquid was distilled (30 C., 1 mm) yielding 12.5 g of a clear liquid which was a mixture of 3,5-difluoro-4-methoxyacetophenone and 3,5-difluoro-4-acetoxyacetophenone in an 85:15 ratio.
The synthetic route of 2,6-Difluoroanisole has been constantly updated, and we look forward to future research findings.
Reference:
Patent; G.D. Searle & Co.; US5756529; (1998); A;,
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Ether | (C2H5)2O – PubChem