Iodine → 3-isobutyl-4,4,6,6-tetramethyl-4,6-dihydrofuro[3,4-d]thiazol-2(3H)-imine

Temperature

60 °C

To a solution of 2,2,5,5-tetramethyldihydrofuran-3(2H)-one (2.0 g, 14.1 mmol, Aldrich) in acetonitrile (10 mL) were added molecular sieves (2.0 g) and 2-methylpropan-1-amine (1.0 mL, 12.8 mmol, Aldrich). The reaction mixture was stirred at 60° C. for 48 hr and then filtered through celite. To the filtrate were added potassium thiocyanate (1.65 g, 17.0 mmol, Aldrich). The reaction mixture was stirred at 60° C. until the solids were dissolved and then iodine (6.5 g, 25.6 mmol, EMD chemicals) was added. The reaction mixture was stirred 60° C. for 48 hr, cooled, concentrated and dissolved in ethyl acetate (15 mL). The solution was washed with sodium metabisulfite 20% (35 mL) by mixing the layers for 30 min. The organic layer was washed twice with HCl 1N (35 mL). The aqueous layers (sodium metabisulfite and HCl) were combined and the pH was adjusted to pH 9 by adding NH4OH and then extracted with ethyl acetate (4×40 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated to obtain the crude product (0.75 g) of the title compound. MS (ESI+) m/z 255 (M+H)+

1. filtrationfiltered through celite
2. stirringThe reaction mixture was stirred at 60° C. until the solids
3. dissolutionwere dissolved
4. stirringThe reaction mixture was stirred 60° C. for 48 hr
5. temperaturecooled
6. concentrationconcentrated
7. dissolutiondissolved in ethyl acetate (15 mL)
8. washThe solution was washed with sodium metabisulfite 20% (35 mL)
9. additionby mixing the layers for 30 min
10. washThe organic layer was washed twice with HCl 1N (35 mL)
11. additionby adding NH4OH
12. extractionextracted with ethyl acetate (4×40 mL)
13. dry with materialThe combined organic extracts were dried (Na2SO4)
14. filtrationfiltered
15. concentrationconcentrated

ORD record

ord-6d03034717fa420dae8f5cdb81c0877b

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07875640B2