Diisopropylamine → 3-(4-Propylbenzoyl)-7-vinylchroman-4-one

온도

0 °C

To a flame-dried 10 mL round-bottom flask under nitrogen charged with butyllithium (2.5 M in hexanes) (0.875 mL, 2.19 mmol) in THF (1 mL) at 0° C. was added diisopropylamine (0.312 mL, 2.19 mmol) dropwise. The solution was stirred at 0° C. for 20 min. The solution was then cooled to −78° C., and 7-vinylchroman-4-one (Preparation 2D, 1.79 M in THF) (1.02 mL, 1.82 mmol) was added dropwise via syringe. The mixture was stirred for 20 min. at −78° C. 4-propylbenzoyl fluoride (0.303 g, 1.823 mmol) in 1 mL of THF was then added dropwise via syringe, and the reaction mixture was stirred at −78° C. for 60 min. and then warmed to room temperature. The reaction was quenched with 1N aqueous hydrochloric acid (5 mL) and extracted with ethyl acetate (3×20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The yellow residue was purified by flash silica gel chromatography using a mixture of ethyl acetate in hexane (5%-12%) to give 3-(4-propylbenzoyl)-7-vinylchroman-4-one (0.179 g, 0.559 mmol, 31% yield). The compound was triturated with methanol with sonication, filtered, washed with methanol, and dried to give 3-(4-propylbenzoyl)-7-vinylchroman-4-one (0.125 g, 0.390 mmol, 21% yield) as a yellow solid. LC/MS M+1=321.2. 1H NMR (500 MHz, DMSO-d6) δ ppm 0.91 (t, 3H), 1.58-1.68 (m, J=7.42, 7.42, 7.42, 7.42, 7.21 Hz, 2H), 2.65 (t, J=7.63 Hz, 2H) 4.71-4.77 (m, 1H), 4.78-4.83 (m, 1H), 5.20 (dd, J=9.16, 4.99 Hz, 1H), 5.47 (d, J=11.10 Hz, 1H), 6.05 (d, J=17.76 Hz, 1H), 6.73-6.82 (m, 1H), 7.17 (s, 1H) 7.24 (dd, J=8.18, 1.25 Hz, 1H), 7.38 (d, J=8.32 Hz, 2H), 7.73 (d, J=8.05 Hz, 1H), and 7.96 (d, J=8.32 Hz, 2H).

1. temperatureThe solution was then cooled to −78° C.
2. stirringThe mixture was stirred for 20 min. at −78° C
3. stirringthe reaction mixture was stirred at −78° C. for 60 min.
4. temperaturewarmed to room temperature
5. customThe reaction was quenched with 1N aqueous hydrochloric acid (5 mL)
6. extractionextracted with ethyl acetate (3×20 mL)
7. washThe organic layer was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe yellow residue was purified by flash silica gel chromatography
11. additiona mixture of ethyl acetate in hexane (5%-12%)

ORD 기록

ord-216547032feb4832bea052b57d15bf00

출처 데이터셋

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09216972B2