Iodine → tert-butyl 3-((5-tert-butyl-2-iminothiazol-3(2H)-yl)methyl)azetidine-1-carboxylate

A mixture of 3,3-dimethylbutanal (3.7 mL, 30 mmol), tert-butyl 3-(aminomethyl)azetidine-1-carboxylate (Astatech, 5 g, 27 mmol), and 8 g of 4 Å molecular sieves (8-12 mesh beads) in acetonitrile (50 mL) was stirred at ambient temperature for 72 h. The material was filtered through Celite with acetonitrile (additional 25 mL) then potassium thiocyanate (3.5 g, 35 mmol) was added and the mixture was warmed to 50° C. Iodine (6.81 g, 26.8 mmol) was added and the mixture stirred at 50° C. for 16 h then was cooled to ambient temperature. The mixture was stirred with 75 mL of 20% aqueous sodium metabisulfite for 1 h then the layers were separated and the aqueous layer was extracted with 3×10 mL CH2Cl2. The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude title compound (6.3 g, 19 mmol, 72% yield) which was carried on without further purification. MS (DCI/NH3) m/z 326 (M+H)+.

1. filtrationThe material was filtered through Celite with acetonitrile (additional 25 mL)
2. temperaturethe mixture was warmed to 50° C
3. stirringthe mixture stirred at 50° C. for 16 h
4. temperaturethen was cooled to ambient temperature
5. customthe layers were separated
6. extractionthe aqueous layer was extracted with 3×10 mL CH2Cl2
7. dry with materialThe combined organics were dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-f0e3aed7ccba4ab3a70f436bfa5f90b9

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865753B2