3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-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:; See reaction.notes.procedure_details.

Procedure: The compound (52) (12.1 g) was reduced with diisobutylaluminum hydride (1.5M, 65.1 ml) in toluene (500 ml) at -78° C. and the obtained crude product was subjected to silicagel column chromatography to give the titled compound (53). Yield: 11.1 g (91%). the obtained crude product

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

Procedure: The compound (51) (12.6 g) was reduced with sodium borohydride (1.25 g) in methanol (400 ml) at 0° C. to give the titled compound (52). Yield: 12.1 g (95.5%).

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

Procedure: The compound (51) (12.6 g) was reduced with sodium borohydride (1.25 g) in methanol (400 ml) at 0° C. to give the titled compound (52). Yield: 12.1 g (95.5%).

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

Procedure: The compound (9-a) was reacted with dimethyl-3,3-difluoro-2-oxoheptylphosphonate (30.0 g) in dichloromethane in the presence of thallium methoxide (8.23 ml). The crude product obtained by the conventional treatment of the reaction mixture was purified on silica gel column to give the titled compound (10-a) [yield:24.4 g (58%)]. The crude product obtained by the conventional treatment of the reaction mixture was purified on silica gel column

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

Procedure: The compound (9-a) was reacted with dimethyl-3,3-difluoro-2-oxoheptylphosphonate (30.0 g) in dichloromethane in the presence of thallium methoxide (8.23 ml). The crude product obtained by the conventional treatment of the reaction mixture was purified on silica gel column to give the titled compound (10-a) [yield:24.4 g (58%)]. The crude product obtained by the conventional treatment of the reaction mixture was purified on silica gel column

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

Procedure: The compound (52) (12.1 g) was reduced with diisobutylaluminum hydride (1.5M, 65.1 ml) in toluene (500 ml) at -78° C. and the obtained crude product was subjected to silicagel column chromatography to give the titled compound (53). Yield: 11.1 g (91%). the obtained crude product

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

Procedure: The compound (51) (12.6 g) was reduced with sodium borohydride (1.25 g) in methanol (400 ml) at 0° C. to give the titled compound (52). Yield: 12.1 g (95.5%).

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

Procedure: Analogously to the procedure of Example 1, the title compound is was prepared from 1.2 g (9.5 nmuol) of hexahydro-cyclopenta[b]furan-2-one, 10 ml of 1 molar lithium bis-(trimethylsilyl)-amide solution in THF and 1.29 g (9.5 mmol) of allyl bromide in 20 ml of THF. Yield: 1.25 g (79%) of a colourless oil. 1H-NMR(200 MHz; [d6]-DMSO): δ[ppm]: 1.47-1.89 (br m,6H), 2.15-2.55 (br m,4H), 4.41 (m,1H), 5.12 (dd,1H), 5.18 (dd,1H), 5.76 (ddt,1H)

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

Procedure: Under argon, 8.7 ml of a 1 molar solution of lithium bis-(trimethylsilyl)-amide in THF are added dropwise to a solution, cooled to −78° C., of 1 g (7.9 mmol) of hexahydro-cyclopenta[b]furan-2-one in 20 ml of THF such that the temp. of the mixture does not exceed −65° C. After the addition has ended, stirring is continued at −78° C. for 10 min, and 1.93 g (8.7 mmol) of naphth-2-ylmethyl bromide are then added in one portion. Immediately afterwards, the cooling bath is removed and the mixture is allowed to warm to room temp. After 16 h of stirring at room temp., the mixture is taken up in water/diethyl ether and the aqueous phase is extracted twice with diethyl ether. The combined organic phases are dried over sodium sulphate and then concentrated. The residue is chromatographed over silica gel (mobile phase: dichloromethane); Yield: 1.2 g, colourless oil, diastereomer mixture: 87:13 (Example 1) 1H-NMR (200 MHz; [d6]-DMSO): δ[ppm]=1.2-1.9 (br m,7H), 2.6 (m,1H), 2.87 (dd, 1H); 2.93 (dd,1H), 4.72/4.75 (m;1H), 7.48-7.55 (m;3H), 7.76 (s;1H), 7.81-7.95 (m;3H). does not exceed −65° C After the addition Immediately afterwards, the cooling bath is removed After 16 h of stirring at room temp. the aqueous phase is extracted twice with diethyl ether The combined organic phases are dried over sodium sulphate concentrated The residue is chromatographed over silica gel (mobile phase: dichloromethane)

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

Procedure: Under argon, 8.7 ml of a 1 molar solution of lithium bis-(trimethylsilyl)-amide in THF are added dropwise to a solution, cooled to −78° C., of 1 g (7.9 mmol) of hexahydro-cyclopenta[b]furan-2-one in 20 ml of THF such that the temp. of the mixture does not exceed −65° C. After the addition has ended, stirring is continued at −78° C. for 10 min, and 1.93 g (8.7 mmol) of naphth-2-ylmethyl bromide are then added in one portion. Immediately afterwards, the cooling bath is removed and the mixture is allowed to warm to room temp. After 16 h of stirring at room temp., the mixture is taken up in water/diethyl ether and the aqueous phase is extracted twice with diethyl ether. The combined organic phases are dried over sodium sulphate and then concentrated. The residue is chromatographed over silica gel (mobile phase: dichloromethane); Yield: 1.2 g, colourless oil, diastereomer mixture: 87:13 (Example 1) 1H-NMR (200 MHz; [d6]-DMSO): δ[ppm]=1.2-1.9 (br m,7H), 2.6 (m,1H), 2.87 (dd, 1H); 2.93 (dd,1H), 4.72/4.75 (m;1H), 7.48-7.55 (m;3H), 7.76 (s;1H), 7.81-7.95 (m;3H). does not exceed −65° C After the addition Immediately afterwards, the cooling bath is removed After 16 h of stirring at room temp. the aqueous phase is extracted twice with diethyl ether The combined organic phases are dried over sodium sulphate concentrated The residue is chromatographed over silica gel (mobile phase: dichloromethane)