(5R)-5-methyl-2-propan-2-ylidenecyclohexan-1-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled with an ice-bath under nitrogen. 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 5% HCl (1 L) and ether (300 mL) 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 water (1 L) and ether (300 mL). 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). The reaction mixture was cooled with an ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled with an ice-bath under nitrogen. 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 5% HCl (1 L) and ether (300 mL) 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). 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 water (1 L) and ether (300 mL). 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). The reaction mixture was cooled with an ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) Then boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled with an ice-bath under nitrogen. 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 5% HCl (1 L) and ether (300 mL) 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). 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 water (1 L) and ether (300 mL). 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). The reaction mixture was cooled with an ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) Then boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 3 L round bottom flask was added (r)-Pulegone (300 g, 1.97 mol), anhydrous NaHCO3 (82 g, 0.99 mol) and Ether (1.5 L). The mixture was cooled to −5° C. ice-salt bath under N2. Then bromine (101 mL, 1.97 mol) was added dropwise over 45 minutes. The mixture was filtered and carefully added dropwise (addition is exothermic in nature) to NaOEt (20 wt %, 4.3 mol) cooled at 0° C. The reaction was allowed to stir with warming to ambient temperature overnight. Then 1 L of 5% HCl and 300 mL of ether was added. The aqueous phase was extracted with ether and the combined organic layers washed with brine, dried with MgSO4 and concentrated. The resulting brown oil diluted with EtOH was added to a warm solution of semicarbazide HCl (150 g, 1.3 mol), NaOAc (150 g, 1.8 mol) and H2O (2 L) to give a brownish solution. The mixture was then refluxed for 3 hours and stirred at ambient temperature overnight. The mixture was treated with 1 L of water and 500 mL of ether. The aqueous phase was extracted with ether. The combined organic layers were dried with MgSO4 and concentrated to give a brown oil. The oil was subject to vacuum distillation, and the title compound (247 g, 64% yield) was collected at 73-76° C. The mixture was filtered carefully added dropwise cooled at 0° C with warming to ambient temperature overnight The aqueous phase was extracted with ether the combined organic layers washed with brine dried with MgSO4 concentrated The resulting brown oil diluted with EtOH to give a brownish solution The mixture was then refluxed for 3 hours stirred at ambient temperature overnight The aqueous phase was extracted with ether The combined organic layers were dried with MgSO4 concentrated to give a brown oil The oil was subject to vacuum distillation

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 3 L round bottom flask was added (r)-Pulegone (300 g, 1.97 mol), anhydrous NaHCO3 (82 g, 0.99 mol) and Ether (1.5 L). The mixture was cooled to −5° C. ice-salt bath under N2. Then bromine (101 mL, 1.97 mol) was added dropwise over 45 minutes. The mixture was filtered and carefully added dropwise (addition is exothermic in nature) to NaOEt (20 wt %, 4.3 mol) cooled at 0° C. The reaction was allowed to stir with warming to ambient temperature overnight. Then 1L of 5% HCl and 300 mL of ether was added. The aqueous phase was extracted with ether and the combined organic layers washed with brine, dried with MgSO4− and concentrated. The resulting brown oil diluted with EtOH was added to a warm solution of semicarbazide HCl (150 g, 1.3 mol), NaOAc (150 g, 1.8 mol) and H2O (2 L) to give a brownish solution. The mixture was then refluxed for 3 hours and stirred at ambient temperature overnight. The mixture was treated with 1 L of water and 500 mL of ether. The aqueous phase was extracted with ether. The combined organic layers were dried with MgSO4 and concentrated to give a brown oil. The oil was subject to vacuum distillation, and the title compound (247 g, 64% yield) was collected at 73-76° C. The mixture was filtered carefully added dropwise cooled at 0° C with warming to ambient temperature overnight The aqueous phase was extracted with ether the combined organic layers washed with brine dried with MgSO4− concentrated The resulting brown oil diluted with EtOH to give a brownish solution The mixture was then refluxed for 3 hours stirred at ambient temperature overnight The aqueous phase was extracted with ether The combined organic layers were dried with MgSO4 concentrated to give a brown oil The oil was subject to vacuum distillation

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 3 L round bottom flask was added (r)-Pulegone (300 g, 1.97 mol), anhydrous NaHCO3 (82 g, 0.99 mol) and Ether (1.5 L). The mixture was cooled to −5° C. ice-salt bath under N2. Then bromine (101 mL, 1.97 mol) was added dropwise over 45 minutes. The mixture was filtered and carefully added dropwise (addition is exothermic in nature) to NaOEt (20 wt %, 4.3 mol) cooled at 0° C. The reaction was allowed to stir with warming to ambient temperature overnight. Then 1L of 5% HCl and 300 mL of ether was added. The aqueous phase was extracted with ether and the combined organic layers washed with brine, dried with MgSO4− and concentrated. The resulting brown oil diluted with EtOH was added to a warm solution of semicarbazide HCl (150 g, 1.3 mol), NaOAc (150 g, 1.8 mol) and H2O (2 L) to give a brownish solution. The mixture was then refluxed for 3 hours and stirred at ambient temperature overnight. The mixture was treated with 1 L of water and 500 mL of ether. The aqueous phase was extracted with ether. The combined organic layers were dried with MgSO4 and concentrated to give a brown oil. The oil was subject to vacuum distillation, and the title compound (247 g, 64% yield) was collected at 73-76° C. The mixture was filtered carefully added dropwise cooled at 0° C with warming to ambient temperature overnight The aqueous phase was extracted with ether the combined organic layers washed with brine dried with MgSO4− concentrated The resulting brown oil diluted with EtOH to give a brownish solution The mixture was then refluxed for 3 hours stirred at ambient temperature overnight The aqueous phase was extracted with ether The combined organic layers were dried with MgSO4 concentrated to give a brown oil The oil was subject to vacuum distillation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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 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 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). The reaction mixture was cooled with ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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 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 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). The reaction mixture was cooled with ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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 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 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). The reaction mixture was cooled with ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). The reaction mixture was cooled with ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). The reaction mixture was cooled with ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled with an ice-bath under nitrogen. Bromine (25.62 mL, 0.5 mmol) was added dropwise over about 30 minutes. The mixture was filtered and added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at about room temperature overnight, and then 5% HCl (1 L) and ether (300 mL) 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). Then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at about room temperature overnight. The mixture was treated with water (1 L) and ether (300 mL). 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). The reaction mixture was cooled with an ice-bath under nitrogen The mixture was filtered cooled bath The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL) Then boiling ethanol (300 mL) was added to give a clear solution The mixture was refluxed for 2.5 hours stirred at about room temperature overnight The aqueous phase was extracted with ether (2×300 mL) The combined organic phase was washed with water dried concentrated The residue was purified by vacuum distillation (73-76° C. at 0.8 mm Hg)