Nitrogen → HCID 178495558, compound

Temperature

0 °C

To a mixture of 3,3,3-trifluoro-2,2-dimethylpropanoic acid (10 g, 64.1 mmol) in CHCl3 (100 mL) cooled to 0° C. was added oxalyl chloride (7.29 mL, 83 mmol) dropwise. The mixture was stirred at 70° C. for 4 h. Then the mixture was concentrated. To a mixture of (E)-4-methoxybut-3-en-2-one (12.83 g, 128 mmol) in THF (100 mL) cooled to −78° C. was added LiHMDS (128 mL, 128 mmol) dropwise under N2. The mixture was stirred at −78° C. for 1 h. Then to the mixture was added a solution of 3,3,3-trifluoro-2,2-dimethylpropanoyl chloride in THF (100 mL) at −78° C. The whole mixture was allowed to warm to rt over 2 h and quenched by NH4Cl (saturated aqueous, 30 mL). THF was removed under vacuum. To the mixture was added H2O (80 mL) and then extracted with EA (100 mL×3). The organic layer was washed with brine (80 mL), dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=2:1). All fractions found to contain product by TLC (PE/EA=2:1, Rf=0.5) were combined to yield an off-white oil of (1E,4Z)-7,7,7-trifluoro-5-hydroxy-1-methoxy-6,6-dimethylhepta-1,4-dien-3-one (1 g, 3.36 mmol, 5.2% yield): 1H NMR (400 MHz, CDCl3): δ 15.90 (s, 1H), 7.65 (d, J=12.4 Hz, 1H), 5.63 (s, 1H), 5.33 (d, J=12.4 Hz, 1H), 3.74 (s, 3H), 1.38 (s, 6H). ES-LCMS m/z 239.1 (M+H).

1. concentrationThen the mixture was concentrated
2. temperaturecooled to −78° C.
3. stirringThe mixture was stirred at −78° C. for 1 h
4. temperatureto warm to rt over 2 h
5. customquenched by NH4Cl (saturated aqueous, 30 mL)
6. customTHF was removed under vacuum
7. additionTo the mixture was added H2O (80 mL)
8. extractionextracted with EA (100 mL×3)
9. washThe organic layer was washed with brine (80 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude material was purified by silica column chromatography (PE/EA=2:1)

ORD record

ord-d92107f834bc4236965d3bfb1b50ba42

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382238B2