Methyl iodide → HCID 13304180, compound

Temperature

-75 °C

3-(4-Chlorophenyl)tetrahydro-2-(3-pyridyl)-4H-1,3-thiazin-4-one, 3.05 g. (0.01 mole), prepared as described in Example 70, supra, was added with mechanical stirring to 40 ml. of anhydrous tetrahydrofuran maintained under a nitrogen atmosphere and then cooled to about -75° C. To the cold solution there was added, over a period of about 15-20 minutes, 4.28 ml. of a hexane solution of n-butyllithium (2.4 molar in hexane), while maintaining the reaction temperature below -70° C. After the addition was complete, the reaction mixture was stirred for about 30 minutes at a temperature of about -75° C., followed by the dropwise addition of 5 ml. of methyl iodide over a period of about 10-15 minutes. The reaction product mixture was stirred overnight while being cooled in a dry iceacetone bath, warming gradually to about 0° C., by morning. A peach-colored solid precipitated during the night. The reaction product mixture was warmed to room temperature and methylene chloride added, forming a red solution. The solution was concentrated in vacuo. The residue thus obtained was redissolved in methylene chloride and the solution was washed twice with cold salt water and dried over anhydrous sodium sulfate. The drying agent was filtered off and the filtrate concentrated in vacuo to leave a residue. The residue was taken up in ethyl acetate and passed through a layer of silica gel (400 ml.). The ethyl acetate solution so treated was concentrated in vacuo, and the oil which remained was dissolved in methylene chloride, treated with decolorizing carbon, filtered, and the filtrate concentrated to dryness in vacuo. The residue thus obtained was dissolved in ethyl ether, and upon cooling a solid crystallized, and was filtered off. The solid had a melting point of about 128°-130° C., and weighed 1.1 g. The solid was identified by NMR spectrum and elemental analyses as 3-(4-chlorophenyl)tetrahydro-5-methyl-2-(3-pyridyl)-4H-1,3-thiazin-4-one. Analyses calculated for C16H15ClN2OS:

1. custom(0.01 mole), prepared
2. additionwas added
3. additionTo the cold solution there was added, over a period of about 15-20 minutes
4. additionAfter the addition
5. stirringthe reaction mixture was stirred for about 30 minutes at a temperature of about -75° C.
6. additionfollowed by the dropwise addition of 5 ml
7. stirringThe reaction product mixture was stirred overnight
8. temperaturewhile being cooled in a dry iceacetone bath
9. temperaturewarming gradually to about 0° C., by morning
10. customA peach-colored solid precipitated during the night
11. temperatureThe reaction product mixture was warmed to room temperature
12. additionmethylene chloride added
13. customforming a red solution
14. concentrationThe solution was concentrated in vacuo
15. customThe residue thus obtained
16. washthe solution was washed twice with cold salt water
17. dry with materialdried over anhydrous sodium sulfate
18. filtrationThe drying agent was filtered off
19. concentrationthe filtrate concentrated in vacuo
20. customto leave a residue
21. concentrationwas concentrated in vacuo
22. dissolutionthe oil which remained was dissolved in methylene chloride
23. additiontreated with decolorizing carbon
24. filtrationfiltered
25. concentrationthe filtrate concentrated to dryness in vacuo
26. customThe residue thus obtained
27. temperatureupon cooling a solid
28. customcrystallized
29. filtrationwas filtered off

ORD record

ord-8d70155565014fe6ac6df89e2dab17e4

Source dataset

uspto-grants-1984_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04482712