With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1197-66-6,2,2,6,6-Tetramethyl-2H-3,5,6-trihydropyran-4-one,as a common compound, the synthetic route is as follows.
A 2 L RBF under light nitrogen flow was charged with 2,2,6,6-tetramethyldihydro-2H-pyran-4(3H)-one (1.00 equiv; 49.10 mL; 43.45 g), (a known compound which may be prepared as described in, for example, MAGNUS, P., et al., ?Synthesis of the ABCD-rings of the insecticidal indole alkaloid nodulisporic acid?, Tet. Lett., 1999, pp 6909-6912, Vol. 40) 2-methyl-THF (375.00 mL; 322.05 g) and DBU (76.67 mL; 77.67 g). The resulting mixture was stirred and cooled to about 2 C. with a water-ice bath. NfsulphF (1.20 equiv; 56.07 mL; 94.20 g) was introduced into a dropping funnel and the NfsulphF was then added to the reaction mixture over 20 minutes, with a light exotherm is observed. After complete addition, the water-ice bath was taken away and the temperature allowed to rise to room temperature. Precipitation was observed to start forming, resulting in a yellow suspension. The yellow suspension was stirred overnight at room temperature and yielded yield a brown suspension. [0249] To the brown suspension was slowly added water (1.12 L; 1.12 kg), with an observed exotherm. The resulting mixture was warmed 44 C., resulting in a multi-phase mixture with good separation (the organic layer was the top layer). The mixture was stirred for 20 minutes and the phases warm separated at about 44 C. The aqueous (orange colored) layer was returned to the RBF, and then extracted with 2-methyl-THF (185.00 mL; 158.88 g) by stirring 20 minutes at 44 C., then warm separating the resulting layers. The organic layers were then combined. Water (190.00 mL; 190.00 g) was added and the resulting mixture stir for 20 minutes, and the resulting layers warm separated at 44 C. The organic layer was then washed second time with water (190.00 mL; 190.00 g), with some white fluffy precipitation observed in the water layer. The organic layer was then evaporated on a rotavap at 45 C. The resulting biphasic residue included a thick brown bottom layer (129.17 g) and light colored material on top. To the residue was added HEPTANE 50% (a mixture of 50% n-heptane, 20% other heptane isomers and 30% methyl cyclohexane; 250.00 mL; 176.75 g), then acetonitrile (19.00 mL; 14.88 g). The resulting mixture was stirred firmly, the acetonitrile was observed to take up the oily layer, resulting in a biphasic system. The mixture was then stirred for 1 hour, the layers separated. The heptane layer was evaporated on a rotovap at 42 C. to yield the title compound as a residue (102.60 g) [0250] Actual Yield: 93.52% 102.60 g, 234.08 mmol [0251] Theoretical Yield: 100% 109.58 g, 250.00 mmol, 1197-66-6
As the paragraph descriping shows that 1197-66-6 is playing an increasingly important role.
Reference£º
Patent; Janssen Pharmaceutica NV; KOLODZIEJCZYK, Krzysztof; Stappers, Alfred Elisabeth; Teleha, Christopher A.; Weerts, Koen Johan Herman; US2014/45789; (2014); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics