Synthetic Route of 67442-07-3, These common heterocyclic compound, 67442-07-3, name is 2-Chloro-N-methoxy-N-methylacetamide, 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.
C. Synthesis of Intermediate 22 [0244] A 3-neck flask was charged with 21 (100 g) and THF (800 mL). The solution was degassed three times by slowly applying vacuum, followed by breaking vacuum with nitrogen. The solution was cooled to -10 C. internal temperature. A solution of 2N i-PrMgCl solution in THF (125 g, 1.04 mole equiv) was added slowly while maintaining internal temperature at -10 C. to 0 C. The resulting mixture was then stirred for 30 minutes at -10 C. until reaction was complete. 2-Chloro-N-methoxy-N-methylacetamide (40.6 g, 1.20 mole equiv) was dissolved in MTBE (122 g, 1.22 wt equiv) and filtered through a 1 mum filter. The MTBE solution of the acetamide was then added slowly to the flask maintaining internal temperature at -10 C. to 0 C. Upon completion of the addition, the internal temperature was adjusted to 0 C. and agitated for 2 hours. After the reaction is complete, 1N HCl (750 g) was added slowly so that the internal temperature did not exceed 20 C. If necessary, the internal temperature was adjusted to 20 C. The layers were separated and the aqueous layer was extracted with MTBE (410 g). The organic layers were combined and dried over MgSO4. The MgSO4 was filtered off and rinsed with THF (200 g). The filtrate and rinse were concentrated under vacuum 10 volumes (1000 mL). Isopropanol (785 g) was added and small amounts of crystals began to form. This slurry was again concentrated under vacuum to 10 volumes (1000 mL). Isopropanol (785 g) was once again added and the slurry was concentrated under vacuum to 10 volumes (1000 mL). The internal temperature was adjusted to 20-25 C. and agitated for ca. 30 minutes. The slurry was filtered and rinsed with isopropanol (100 g) then dried under vacuum to provide 62.28 g (70.8%, 98% purity by HPLC) of the product 22 as an off-white to pale yellow solid. 1H NMR (400 MHz, CDCl3, delta): 8.19 (s, 1H), 8.12 (d, J=7.8 Hz, 1H), 7.82 (s, 1H), 7.67 (d, J=8.0 Hz, 2H), 7.52 (d, J=7.8 Hz, 1H), 4.71 (s, 2H). 19F NMR (376 MHz, CDCl3) delta -111.4 (s, 2F).
Statistics shows that 2-Chloro-N-methoxy-N-methylacetamide is playing an increasingly important role. we look forward to future research findings about 67442-07-3.
Reference:
Patent; Scott, Robert William; Wang, Fang; Shi, Bing; Mogalian, Erik; US2013/324496; (2013); A1;,
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