Diisopropylethylamine → (Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-one

Temperature

0 °C

In a 25-mL, three-necked, round-bottomed flask equipped with nitrogen inlet and a rubber septum, (Z)-3-iodoacrylic acid (0.250 g, 1.0 eq.) was dissolved in DCM (10 mL, 40 V). The reaction mixture was cooled to 0° C., and DIPEA (0.168 g, 1.1 eq), HATU (0.494 g, 1.1 eq) and 3,3-difluoroazetidine hydrochloride (0.179 g, 1.1) were added. The reaction mixture was stirred at 0° C. for 2-3 hr. The progress of the reaction was followed by TLC analysis on silica gel with 40% ethyl acetate in hexane. The reaction mixture was filtered and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 0.3 g of crude compound which was purified by column chromatography using silica 60/120 using 40% ethyl acetate in hexane as mobile phase. The column (5×10 cm) was packed in 5% ethyl acetate in hexane and started eluting in ethyl acetate in gradient manner starting with fraction collection (50-mL fractions) from 20% to 30% ethyl acetate in hexane. Compound started eluting with 20% ethyl acetate in hexane. Fractions containing such TLC profile were combined to obtain 0.18 g of desired compound (yield 52.33%). Mass: [M+H]+: 273.8.

1. customIn a 25-mL, three-necked, round-bottomed flask equipped with nitrogen inlet
2. filtrationThe reaction mixture was filtered
3. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
4. customto afford 0.3 g of crude compound which
5. customwas purified by column chromatography
6. washstarted eluting in ethyl acetate in gradient manner
7. customstarting with fraction collection (50-mL fractions) from 20% to 30% ethyl acetate in hexane
8. washCompound started eluting with 20% ethyl acetate in hexane
9. additionFractions containing such TLC profile

ORD record

ord-96a4cacc646c4692b02db6f9cbbf6682

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999996B2