Isobutylbenzene → HCID 13647430, compound

Temperature

0 °C

To a dry 3-necked round-bottom flask under argon atmosphere equipped with a dropping funnel, septum and magnetic stir bar was added 12.6 mL (80 mmol) of isobutylbenzene, 12.3 mL (80 mmol) of diethyl ketomalonate (DEOM) and 40 mL of CH2Cl2. The flask was cooled with stirring to 0° C. followed by the dropwise addition of 11.7 mL (100 mmol) of SnCl4. The yellow reaction mixture was allowed to warm slowly to room temperature and after 3 hours the reaction was quenched by pouring the suspension into a mixture of 50 g of ice and 50 mL of 5% aqueous HCl and extracted with ether (3×100 mL). The ether layers were combined and washed with water (2×50 mL), 25 mL of brine, dried over MgSO4 and concentrated. The crude diester was diluted with 120 mL of H2O and 18 g (320 mmol) of KOH was added. The orange reaction mixture was stirred at 90° C. for 1.5 h, and washed with 2×30 mL of ether. Decarboxylation was effected by adjusting the pH to 1 with concentrated HCl and warming to 90° C. for 45 minutes. The pH of the solution was monitored and additional HCl was added as needed to maintain the pH of the solution below 2. The two phase system was extracted with 3×75 mL of ether and the combined ether layers were washed with 25 mL of H2O, 25 mL of brine, dried over MgSO4 and concentrated leaving 12.3 g (73.8%) of a white solid which was not purified, but directly resolved into individual enantiomers.

1. customTo a dry 3-necked round-bottom flask under argon atmosphere equipped with a dropping funnel
2. temperatureThe flask was cooled
3. temperatureto warm slowly to room temperature and after 3 hours the reaction
4. customwas quenched
5. additionby pouring the suspension
6. additioninto a mixture of 50 g of ice and 50 mL of 5% aqueous HCl
7. extractionextracted with ether (3×100 mL)
8. washwashed with water (2×50 mL), 25 mL of brine
9. dry with materialdried over MgSO4
10. concentrationconcentrated
11. additionwas added
12. stirringThe orange reaction mixture was stirred at 90° C. for 1.5 h
13. washwashed with 2×30 mL of ether
14. temperaturewarming to 90° C. for 45 minutes
15. additionadditional HCl was added
16. temperatureto maintain the pH of the solution below 2
17. extractionThe two phase system was extracted with 3×75 mL of ether
18. washthe combined ether layers were washed with 25 mL of H2O, 25 mL of brine
19. dry with materialdried over MgSO4
20. concentrationconcentrated

ORD record

ord-daa1177847ee4658b66683847d922bef

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05504108