Epichlorohydrin → HCID 53630940, Verbindung

A solution of (4R)-1,3-thiazolidin-4-ylmethanol (0.300 g, 2.52 mmol) in 2-(chloromethyl)oxirane (2.0 mL, 25.5 mmol) was heated under nitrogen to 40° C. for 12 h. The solution was then cooled to room temperature and 2-(chloromethyl)oxirane was removed in vacuo. The crude intermediate was cooled in ice, and was taken up in 2.0 mL of concentrated sulfuric acid. The resulting mixture was heated to 200° C. for 0.5 h then poured carefully onto wet ice, which was allowed to melt. The aqueous solution was carefully made basic using solid sodium bicarbonate and the resulting mixture was filtered using water and 10% methanol in ethyl acetate as eluent. The layers were separated and the aqueous layer was extracted with 10% methanol in ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give 11.6 mg (2.4% yield) of crude (8aR)-6-(chloromethyl)tetrahydro-1H-[1,3]thiazolo[4,3-c][1,4]oxazine as a mixture of diastereomers which was directly taken on to the next step.

1. custom2-(chloromethyl)oxirane was removed in vacuo
2. temperatureThe crude intermediate was cooled in ice
3. temperatureThe resulting mixture was heated to 200° C. for 0.5 h
4. additionthen poured carefully onto wet ice, which
5. filtrationthe resulting mixture was filtered
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with 10% methanol in ethyl acetate
8. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD-Eintrag

ord-60783d937eda4c2dab4f4f7e14795831

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08497284B2