Synthetic Route of 928-92-7, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 928-92-7 as follows.
Example 5; Methyl 5-methyl-3,4-dihydro-2H-pyrano [2,3-c] pyridine-6-carboxylate(a) (is)-Methyl 2-((2-(hex-4-en-l-yloxy)-2-oxoethyl)amino)-2-oxoacetateTo a vessel maintained at 40 ¡ãC was charged CDI (2.75 g, 0.95 eq) and TBME (9 mL). To this mixture was added with stirring a solution of N-(?-butoxycarbonyl)glycine (3.1 g, 1.0 eq) dissolved in TBME (12 mL) over 30 min. Stirring was continued for an additional 30 min, whereupon trans-4-hexen-l-ol (1.7 g, 0.95 eq) was added over 30 min. The mixture was maintained with stirring at 40 ¡ãC for an additional 3.5 h, then cooled to ambient temperature and stirred a further 14 h. The mixture was washed with IN HQ (2 x 7.8 mL) then water (1 x 7.8 mL). The organic layer was dried over a2S04, filtered and concentrated to give (.pound.)-hex-4-en-l-yl 2-((tert-butoxycarbonyl)amino)acetate as an oil. The oil was dissolved in DCM (12 mL) and 4.0 M HC1 in dioxane (2.8 mL) was added drop-wise. The mixture was stirred at ambient temperature for 1.5 h then the mixture was heated to 35 ¡ãC and stirred for 3 h. 4.0 M HC1 in dioxane (2.8 mL) was added drop-wise. After 6 h at 35 ¡ãC a further dose of 4.0 M HC1 in dioxane (2.8 mL) was added drop-wise and the mixture was stirred for a further 4 h. The mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. A portion of the residue (1.0 g) was dissolved in DCM (8 mL) and methyl 2-chloro-2-oxoacetate (0.63 g) was added. Triethylamine (1.0 g) was added drop-wise over 20 min. The mixture was stirred for 1 h before being quenched by IN HC1 (2.5 mL) to form a biphasic mixture. The layers were separated and the organic layer was washed with IN HCl (1 x 2.5 mL), water (1 x 2.5 mL) and concentrated under reduced pressure to provide an oil. Flash columnchromatography (S1O2, 10->60percent EtO Ac/Hex gradient) provided the title compound as an oil as a 95:5 mixture of trans:cis isomers. XH NMR (300 MHz, CDCI3) delta ppm 7.57 (s, 1 H), 5.31-5.55 (m, 2 H), 4.17 (t, J=6.69 Hz, 2 H), 4.12 (d, J=5.51 Hz, 2 H), 3.92 (s, 3 H), 1.97-2.10 (m, 2 H), 1.67-1.77 (m, 2 H), 1.62-1.67 (m, 3 H); 13C NMR (75 MHz, CDCI3) delta ppm 168.60, 160.35, 156.28, 129.49, 126.12, 65.34, 53.68, 41.47, 28.62, 28.17, 17.84; HRMS (M+H) m/z, calcd for CnH18N05, 244.1185; found 244.1 187.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,928-92-7, its application will become more common.
Reference:
Patent; GLAXO GROUP LIMITED; SISKO, Joseph; MANS, Douglas; YIN, Hao; WO2012/12391; (2012); A2;,
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