Diphosgene → HCID 86631925, compound

5-Methylthiazol-2-amine (571 mg, 5.00 mmol) was dissolved into dichloromethane (30 mL) and cooled to near −45° C. Diphosgene (360 μL, 3.0 mmol) was added rapidly over a second or two, and the mixture was stirred for 5 minutes before diisopropylethylamine (1.74 mL, 10 mmol) was added. The solution was stirred for another 30 minutes, 3-fluorobenzyl-methylamine (1.03 mL, 7.5 mmol) was added, and after another couple of minutes, the cold bath was removed. When the reaction solution had warmed to near room temperature, it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL). The aqueous phase was separated and back-extracted with dichloromethane, and the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL). The aqueous phase was separated and back-extracted with dichloromethane. The combined organic phases were dried (sodium sulfate), concentrated, and chromatographed on acidic alumina (ethyl acetate/hexanes) to give the title compound.

1. temperaturecooled
2. customto near −45° C
3. additionwas added
4. customafter another couple of minutes, the cold bath was removed
5. customit was quenched with 1 M aqueous potassium phosphate monobasic (15 mL)
6. customThe aqueous phase was separated
7. extractionback-extracted with dichloromethane
8. washthe combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL)
9. customThe aqueous phase was separated
10. extractionback-extracted with dichloromethane
11. dry with materialThe combined organic phases were dried (sodium sulfate)
12. concentrationconcentrated
13. customchromatographed on acidic alumina (ethyl acetate/hexanes)

ORD record

ord-cbf1c44c12704b57a62b7916538e7867

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383657B2