3a,4,5,6,7,7a-hexahydro-3H-1-benzofuran-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, a solution of diisopropylamine (3.36 ml, 24 mmol) in 20 ml of dry THF was cooled to 0° C. and admixed with butyllithium (9.6 ml, 24 mmol, 2.5 M in hexane). The solution was stirred with ice-cooling for 15 min, cooled to −78° C. and admixed with a solution of hexahydro-benzofuran-2-one (2.8 g, 20 mmol) in 10 ml of THF. This mixture was stirred at −78° C. for 1 h, and a solution of 2-bromomethylnaphthalene (5.31 g, 24 mmol) in 20 ml of THF was then added. The mixture was stirred at −78° C. for another 2 h and then at room temperature overnight. Water was then added, the organic solvent was removed under reduced pressure and the aqueous phase was extracted with MTBE. The combined ether phases were dried over magnesium sulphate, filtered and concentrated. Purification was carried out by column chromatography. Yield: 2.5 g (44.6%). Rf (cyclohexane/ethyl acetate 3:1)=0.69, Rf (cyclohexane/ethyl acetate 1:1)=0.83 MS (CI): m/e=281 [M+H+] cooling for 15 min This mixture was stirred at −78° C. for 1 h The mixture was stirred at −78° C. for another 2 h at room temperature overnight the organic solvent was removed under reduced pressure the aqueous phase was extracted with MTBE The combined ether phases were dried over magnesium sulphate filtered concentrated Purification

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, a solution of diisopropylamine (3.36 ml, 24 mmol) in 20 ml of dry THF was cooled to 0° C. and admixed with butyllithium (9.6 ml, 24 mmol, 2.5 M in hexane). The solution was stirred with ice-cooling for 15 min, cooled to −78° C. and admixed with a solution of hexahydro-benzofuran-2-one (2.8 g, 20 mmol) in 10 ml of THF. This mixture was stirred at −78° C. for 1 h, and a solution of 2-bromomethylnaphthalene (5.31 g, 24 mmol) in 20 ml of THF was then added. The mixture was stirred at −78° C. for another 2 h and then at room temperature overnight. Water was then added, the organic solvent was removed under reduced pressure and the aqueous phase was extracted with MTBE. The combined ether phases were dried over magnesium sulphate, filtered and concentrated. Purification was carried out by column chromatography. Yield: 2.5 g (44.6%). Rf (cyclohexane/ethyl acetate 3:1)=0.69, Rf (cyclohexane/ethyl acetate 1:1)=0.83 MS (CI): m/e=281 [M+H+] cooling for 15 min This mixture was stirred at −78° C. for 1 h The mixture was stirred at −78° C. for another 2 h at room temperature overnight the organic solvent was removed under reduced pressure the aqueous phase was extracted with MTBE The combined ether phases were dried over magnesium sulphate filtered concentrated Purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Oxocyclohexylacetic acid (31.2 g, 200 mmol) is dissolved in 125 ml of 0.2 N aqueous sodium hydroxide solution and, at room temperature, added dropwise to a solution of sodium borohydride (18.9 g, 500 mmol) in 150 ml of 0.2 N aqueous sodium hydroxide solution. The mixture is stirred for 20 h and then cooled to 0° C. and carefully acidified with 6 N HCl. The strongly acidic solution is then heated at 100° C. for 30 min and subsequently stirred overnight. The cold mixture is then extracted with MTBE, and the combined ether phases are washed with 5% strength sodium carbonate solution and sat. NaCl solution, dried over magnesium sulphate, filtered and concentrated. Purification is carried out by distillation (b.p.: 75° C./0.01 mm). Yield: 22.9 g (81.7%). MS (CI): m/e=141 [M+H+] The strongly acidic solution is then heated at 100° C. for 30 min and subsequently stirred overnight The cold mixture is then extracted with MTBE the combined ether phases are washed with 5% strength sodium carbonate solution and sat. NaCl solution dried over magnesium sulphate filtered concentrated Purification is carried out by distillation (b.p.: 75° C./0.01 mm)