HCID 23277935, compound → HCID 58600553, compound

Temperature

48 °C

A 100 mL, 3-necked flask equipped with an overhead stirrer, reflux condenser and pressure equalizing addition funnel was charged with 2c (10.0 g, 60.5 mmol), THF (60 mL) and CuCl (70 mg, 1 mol %) and the stirrer was started. The mixture was heated to 48° C. and the pressure equalizing addition funnel was charged with PhMgCl (2M in THF, 13 mL). This solution was added slowly while maintaining an internal temperature of 48-51° C. The reaction was stirred at 48-51° C. for an additional 30 minutes until the GC analysis indicated the consumption of 2c (<1.0%) and the reaction mixture was cooled to ambient temperature. The reaction was quenched by slow addition to a cooled solution of saturated aqueous ammonium chloride in water (50/50 v/v, 100 mL) while maintaining the temperature below 20° C. Heptanes (100 mL) was used to rinse the reactor and the rinse solution was transferred to the quenched reaction mixture. The mixture was agitated for 15 minutes, allowed to separate for 30 minutes then the aqueous phase was discarded. The organic phase washed with deionized water (30 mL) and the organic phase concentrated under reduced pressure to give an oil. The residue was dissolved in heptanes (100 mL) and the solution was concentrated under reduced pressure. The residue was crystallized from methyl tert-butyl ether (1 g/3 mL), filtered and dried to give 6c as white needles (10.2 g; 74.8% yield), with 99.90% GC purity containing 0.06% 8c. Mp 86-88° C. 1H NMR (300 MHz, CDCl3) δ 7.32-7.17 (m, 5H), 3.66 (d, J=6.4 Hz, 3H), 3.50-3.83 (m, 1H), 2.71 (d, J=6.6 Hz, 2H), 2.45 (m, 1H), 1.15 (d, J=6.6 Hz, 3H).

1. customA 100 mL, 3-necked flask equipped with an overhead stirrer
2. temperaturereflux condenser
3. additionaddition funnel
4. additionaddition funnel
5. additionThis solution was added slowly
6. temperaturewhile maintaining an internal temperature of 48-51° C
7. customthe consumption of 2c (<1.0%)
8. temperaturethe reaction mixture was cooled to ambient temperature
9. customThe reaction was quenched by slow addition to a cooled solution of saturated aqueous ammonium chloride in water (50/50 v/v, 100 mL)
10. temperaturewhile maintaining the temperature below 20° C
11. washto rinse the reactor
12. customthe rinse solution was transferred to the quenched reaction mixture
13. stirringThe mixture was agitated for 15 minutes
14. customto separate for 30 minutes
15. washThe organic phase washed with deionized water (30 mL)
16. concentrationthe organic phase concentrated under reduced pressure
17. customto give an oil
18. concentrationthe solution was concentrated under reduced pressure
19. customThe residue was crystallized from methyl tert-butyl ether (1 g/3 mL)
20. filtrationfiltered
21. customdried

ORD record

ord-c64b9a43258f45cea9d9db94ca45e69d

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321794B2