Synthetic Route of 608-28-6, A common heterocyclic compound, 608-28-6, name is 2-Iodo-1,3-dimethylbenzene, molecular formula is C8H9I, 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.
3-(2,6-Dimethylphenyl)prop-2-yn-1 -ol (32). A 500 mL 3-neck flask fitted with a stir- bar, condenser, and Ar inlet was charged with 2,6-dimethyliodobenzene (21 .6 g, 93.1 mmol), propargyl alcohol (6.78 g, 7.15 mL, 121 mmol), /’Pr2NH (100 mL), and THF (100 mL). The resultant solution was sparged with Ar for 10 min, then Pd(PPh3) (1 .00 g, 0.93 mmol) and Cul (350 mg, 1 .86 mmol) were added. This mixture was heated at 50 C for 1 .5 hr. HPLC analysis showed the reaction to be incomplete. 8 mL more propargyl alcohol was added and the mixture was heated at reflux overnight. The reaction was still incomplete by HPLC analysis. Another 10 mL propargyl alcohol, 500 mg Pd(PPh3) , and 200 mg Cul were added, and the mixture was refluxed for 6 hr. Another 8 mL portion of propargyl alcohol was then added, and the reaction was continued at reflux overnight. The mixture was then cooled, and the solids were filtered off and rinsed with EtOAc (200 mL). The filtrate was concentrated to a dark oil and partitioned with CH2CI2 (500 mL) and saturated NH4CI (250 mL). The organic phase was washed with saturated aqueous NH CI (250 mL) and brine (200 mL) and filtered through phase separation paper. The solution was then filtered through a plug of silica gel. The silica gel was rinsed with CH2CI2 (1 2 L). The combined filtrate was concentrated to 8.5 g of a brown oil. The crude material was chromatographed on silica gel with the product eluting with 10-12% EtOAc in hexanes. The combined fractions were concentrated in vacuo, taken up in CH2CI2 (200 mL), and washed with 5% aqueous Na2S2O3 (200 mL) then brine (200 mL). The solution was filtered through phase separation paper and concentrated in vacuo to give 5.0 g of 32 as an orange solid (32%). 1H NMR (60 MHz, CDCI3): delta 7.3-6.8 (m, 3H), 4.5 (s, 2H), 2.8 (s, 1 H), 2.4 (s, 6H) ppm. HPLC analysis (5:10:85 H2O:A1 :MeOH) showed a purity of greater than 99% with a retention time of 3.7 min
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; ALLERGAN, INC.; EHRING, George R.; GARST, Michael E.; AVEY, JR., Alfred A.; DOLBY, Lloyd J.; ESFANDIARI, Shervin; MACKENZIE, Vivian R.; MARSDEN, Jeremiah A.; MUCHMORE, David C.; WO2013/101926; (2013); A1;,
Iodide – Wikipedia,
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