Potassium Carbonate → 2,5,6,8-Tetrahydro-3H-imidazo[2,1-c][1,4]thiazine

A solution of 23.4 g. (0.20 moles) of 3-thiomorpholinone in 150 ml. dry CH2Cl2 is added dropwise with stirring to a solution of 44 grams of triethyloxonium fluoroborate in 100 ml. of CH2Cl2 maintained at 0°-5°C. Stirring is continued for six hours as temperature is allowed to come to 25°C; K2CO3 (46 g.) is added and the methylene chloride solution is decanted and the residue of K2CO3 is washed with CH2Cl2. The combined organic solutions are dried over anhydrous K2CO3, filtered and solvent evaporated. Distillation of the concentrate gives 17.9 g. of the lactam ether. The lactam ether is added to a solution of 24.6 grams (0.12 moles) of 2-bromo-ethylamine hydrobromide in 150 ml. absolute ethanol and the resulting solution heated on a steam bath for two hours. The solvent is evaporated and the residue washed with ether. The resulting crystalline material is washed with acetone and air dried under suction. The crude crystalline product (28.5 g.) is dissolved in 200 ml. ethanol and sodium methoxide (.07 mole in 50 ml. methanol is added; the resulting solution is heated under reflux with stirring for two hours prior to evaporation of the solvent under reduced pressure. To the residue is added 75 ml. water and the solution made basic with potassium carbonate; the basic solution is extracted with chloroform (3 × 100 ml.). The combined extracts are dried over anhydrous Na2SO4, filtered and the solvent evaporated. Distillation of the concentrate gives 2,3,5,6-tetrahydro-8H-imidazo[2,1-c] [1,4] thiazine (11.3 g.). The hydrochloride and oxalate salts are prepared, respectively, by dissolving 1 g. of the product in the minimum volume of absolute ethanol at 45°C. and adding dropwise an aqueous 1 molar solution of the respective acid; the resulting salts are collected by filtration, washed with ethanol and dried.

1. customto come to 25°C
2. customthe methylene chloride solution is decanted
3. washthe residue of K2CO3 is washed with CH2Cl2
4. dry with materialThe combined organic solutions are dried over anhydrous K2CO3
5. filtrationfiltered
6. customsolvent evaporated
7. distillationDistillation of the concentrate
8. customgives 17.9 g
9. customThe solvent is evaporated
10. washthe residue washed with ether
11. washThe resulting crystalline material is washed with acetone and air
12. customdried under suction
13. dissolutionThe crude crystalline product (28.5 g.) is dissolved in 200 ml
14. additionmethanol is added
15. temperaturethe resulting solution is heated
16. temperatureunder reflux
17. stirringwith stirring for two hours
18. customto evaporation of the solvent under reduced pressure
19. additionTo the residue is added 75 ml
20. extractionthe basic solution is extracted with chloroform (3 × 100 ml.)
21. dry with materialThe combined extracts are dried over anhydrous Na2SO4
22. filtrationfiltered
23. customthe solvent evaporated
24. distillationDistillation of the concentrate

ORD record

ord-29af3159bde44b21b43933d85305745b

Source dataset

uspto-grants-1976_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US03973017