反应详情

To a 1 L round-bottom flask were added (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL). The reaction mixture was cooled with ice-bath under nitrogen. The bromine (25.62 mL, 0.5 mmol) was added dropwise over 30 minutes. The mixture was filtered and carefully added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at room temperature overnight and then 1 L of 5% HCl and 300 mL of ether were added. The aqueous phase was extracted with ether (2×300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL), and then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at room temperature overnight. The mixture was treated with 1 L of water and 300 mL of ether. The aqueous phase was extracted with ether (2×300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg) to give (2R)-ethyl 2-methyl-5-(propan-2-ylidene)cyclopentanecarboxylate (63 g, 64%). 1H NMR (CDCl3, 400 MHz) δ 4.13 (m, 2H), 3.38 (d, J=16 Hz, 0.5H), 2.93 (m, 0.5H), 2.50-2.17 (m, 2H), 1.98 (m, 1H), 1.76 (m, 1H), 1.23 (m, 6H), 1.05 (m, 6H).

1. temperatureThe reaction mixture was cooled with ice-bath under nitrogen
2. filtrationThe mixture was filtered
3. temperaturecooled bath
4. extractionThe aqueous phase was extracted with ether (2×300 mL)
5. washThe combined organic phase was washed with water
6. customdried
7. concentrationconcentrated
8. additionThe residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL)
9. additionboiling ethanol (300 mL) was added
10. customto give a clear solution
11. temperatureThe mixture was refluxed for 2.5 hours
12. stirringstirred at room temperature overnight
13. extractionThe aqueous phase was extracted with ether (2×300 mL)
14. washThe combined organic phase was washed with water
15. customdried
16. concentrationconcentrated
17. distillationThe residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)