Potassium Carbonate → 2-(4-Chlorophenyl)-4,4-dimethyl-1-cyclohexene-1-carboxaldehyde

온도

20 °C

To a 250 mL pressure bottle were charged 2-chloro-4,4-dimethylcyclohex-1-enecarbaldehyde (10.00 g), tetrabutylammonium bromide (18.67 g), and acetonitrile (10 mL). The mixture was stirred at 20° C. for 5 min. 21.0 wt % K2CO3 aq. solution (76.0 g) was added. The mixture was stirred at room temperature (rt) for NLT 5 min. followed by addition of 4-chlorophenylboronic acid (9.53 g) all at once. The mixture was evacuated and purged with N2 for three times. Palladium acetate (66 mg, 0.5 mol %) was added all at once under N2. The reaction mixture was evacuated and purged with N2 for three times (an orange colored mixture). The bottle was back filled with N2 and heated to ˜35° C. in an oil bath (bath temp ˜35° C.). The mixture was stirred at 30° C. overnight (15 hours). The reaction mixture was cooled to RT, and pulled IP sample from the upper organic phase for reaction completion, typically starting material <2% (orange colored mixture). Toluene (100 mL) and 5% NaHCO3-2% L-Cysteine aq. solution (100 mL) were added. The mixture was stirred at 20° C. for 60 min. The mixture was filtered through a pad of Celite to remove black solid, rinsing the flask and pad with toluene (10 mL). The upper organic phase was washed with 5% NaHCO3 aq. solution-2% L-Cysteine (100 mL) once more. The upper organic phase was washed with 25% brine (100 mL). The organic layer (105.0 g) was assayed (118.8 mg/g, 12.47 g product assayed, 87% assayed yield), and concentrated to ˜1/3 volume (˜35 mL). The product solution was directly used in the next step without isolation. However, an analytical sample was obtained by removal of solvent to give a brown oil. 1HNMR (CDCl3): δ 1.00 (s, 6H), 1.49 (t, J=6.6 Hz, 2H), 2.28 (t, J=2.1 Hz, 2H), 2.38 (m, 2H), 7.13 (m, 2H), 7.34 (m, 2H), 9.47 (s, 1H).

1. stirringThe mixture was stirred at room temperature (rt) for NLT 5 min.
2. customThe mixture was evacuated
3. custompurged with N2 for three times
4. additionPalladium acetate (66 mg, 0.5 mol %) was added all at once under N2
5. customThe reaction mixture was evacuated
6. custompurged with N2 for three times (an orange colored mixture)
7. additionThe bottle was back filled with N2
8. temperatureheated to ˜35° C. in an oil bath (bath temp ˜35° C.)
9. stirringThe mixture was stirred at 30° C. overnight (15 hours)
10. temperatureThe reaction mixture was cooled to RT
11. customfor reaction completion, typically starting material <2% (orange colored mixture)
12. stirringThe mixture was stirred at 20° C. for 60 min
13. filtrationThe mixture was filtered through a pad of Celite
14. customto remove black solid
15. washrinsing the flask and pad with toluene (10 mL)
16. washThe upper organic phase was washed with 5% NaHCO3 aq. solution-2% L-Cysteine (100 mL) once more
17. washThe upper organic phase was washed with 25% brine (100 mL)

ORD 기록

ord-e2f70f9ebf394ced8dada0612290c8f6

출처 데이터셋

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09238652B2