Methyl iodide → HCID 58711973, Verbindung

Temperatur

40 °C

To a mechanically stirred solution of tert-butyl-2-[(aminocarbonothioyl)hydrazono]-2-(1,3-dithian-2-yl)-1-methylethylcarbamate (Intermediate 2) (600 g, 1.6 mol) in acetonitrile (11 L) and water (1.3 L) was added calcium carbonate (490 g, 4.9 mol) followed by slow addition of iodomethane (2.3 kg, 16 mol) using an addition funnel. After the addition was complete, the solution was heated to 40° C. for 24 hours. The solution was allowed to cool to room temperature and concentrated under reduced pressure until about 1.5 L remained. Water (1.0 L) was added to the solution and the product was extracted with ethyl acetate (6×1 L). The combined extracts were washed with water (4×1 L) and brine (1 L). The solution was dried with magnesium sulfate, filtered and concentrated until a red oil remained (190 g). The oil was dissolve in dichloromethane (250 mL) and 25 mL of this solution was loaded into a RediSep silica gel cartridge (330 g; ISCO) and subjected to a gradient elution using dichlormethane to dichloromethane:ethyl acetate (70:30). The separation was repeated in 25 mL portions until all of the solution was consumed. The appropriate (higher Rf) fractions were combined and concentrated under reduced pressure to give tert-butyl 1-[3-(methylthio)-1,2,4-triazin-6-yl]ethylcarbamate (74 g) as a yellow solid. 1H NMR (CDCl3): δ8.41 (s, 1H), 5.35 (br, 1H), 4.99 (br, 1H), 2.67 (s, 3H), 1.57 (d, J=6.9 Hz, 3H), 1.42 (s, 9H).). MS m/z 271 (M+1). Additionally, the appropriate (lower Rf) fractions were combined and concentrated under reduced pressure to give the isomer tert-butyl 1-[3-(methylthio)-1,2,4-triazin-5-yl]ethylcarbamate (11 g) as a gold oil. 1H NMR (CDCl3): δ8.94 (s, 1H), 5.23 (br, 1H), 4.80 (br, 1H), 2.67 (s, 3H), 1.47 (d, J=7.2 Hz, 3H), 1.43 (s, 9H). MS m/z 271 (M+1).

1. additionAfter the addition
2. temperatureto cool to room temperature
3. concentrationconcentrated under reduced pressure until about 1.5 L
4. additionWater (1.0 L) was added to the solution
5. extractionthe product was extracted with ethyl acetate (6×1 L)
6. washThe combined extracts were washed with water (4×1 L) and brine (1 L)
7. dry with materialThe solution was dried with magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated until a red oil
10. dissolutionThe oil was dissolve in dichloromethane (250 mL)
11. washsubjected to a gradient elution
12. customThe separation
13. customwas consumed
14. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-2ce424128b294b80ae1e8736348be5dd

Quelldatensatz

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07462614B2