(1R,2R)-2-pent-4-enylcyclopropan-1-ol

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution (0.45 M) of the preceding compound in hexane was treated with a solution (15%) of Et2Zn (1.2 eq) in toluene, and the resulting solution was cooled in an ice bath. Diiodomethane (1.2 eq) was added dropwise, then the solution was stirred for 1 h before being warmed to 20° C. Pyridine (6 eq) was added, and the slurry was stirred for 15 min then poured onto petroleum ether. The mixture was filtered repeatedly through CELITE until a transparent solution was obtained. This mixture was concentrated at 100 mbar, and the solution that remained (that contained trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane, toluene and pyridine) was further diluted with THF. The mixture was cooled to 0° C. then treated dropwise with a solution (1 M) of TBAF (1.2 eq) in THF. After 10 min, the mixture was allowed to warm to 20° C., and after a further 1 h was poured into H2O. The aqueous phase was extracted with EtOAc, and the combined organic extracts were washed with brine then dried. Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether) to furnish the title compound (71%) as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.85-5.75 (m, 1H), 5.00 (dd, J=17.1, 1.6 Hz, 1H), 4.94 (br d, J=10.4 Hz, 1H), 3.20 (apparent dt, J=6.4, 2.5 Hz, 1H), 2.10-2.04 (m, 2H), 1.52-1.44 (m, 2H), 1.29-1.19 (m, 1H), 1.15-1.07 (m, 1H), 0.95-0.87 (m, 1H), 0.71-0.66 (m,1H), 0.31 (apparent q, J=6.0 Hz, 1H). the resulting solution was cooled in an ice bath the slurry was stirred for 15 min then poured onto petroleum ether The mixture was filtered repeatedly through CELITE until a transparent solution was obtained This mixture was concentrated at 100 mbar was further diluted with THF The mixture was cooled to 0° C. After 10 min to warm to 20° C. The aqueous phase was extracted with EtOAc the combined organic extracts were washed with brine then dried Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution (0.45 M) of the preceding compound in hexane was treated with a solution (15%) of Et2Zn (1.2 eq) in toluene, and the resulting solution was cooled in an ice bath. Diiodomethane (1.2 eq) was added dropwise, then the solution was stirred for 1 h before being warmed to 20° C. Pyridine (6 eq) was added, and the slurry was stirred for 15 min then poured onto petroleum ether. The mixture was filtered repeatedly through CELITE until a transparent solution was obtained. This mixture was concentrated at 100 mbar, and the solution that remained (that contained trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane, toluene and pyridine) was further diluted with THF. The mixture was cooled to 0° C. then treated dropwise with a solution (1 M) of TBAF (1.2 eq) in THF. After 10 min, the mixture was allowed to warm to 20° C., and after a further 1 h was poured into H2O. The aqueous phase was extracted with EtOAc, and the combined organic extracts were washed with brine then dried. Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether) to furnish the title compound (71%) as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.85-5.75 (m, 1H), 5.00 (dd, J=17.1, 1.6 Hz, 1H), 4.94 (br d, J=10.4 Hz, 1H), 3.20 (apparent dt, J=6.4, 2.5 Hz, 1H), 2.10-2.04 (m, 2H), 1.52-1.44 (m, 2H), 1.29-1.19 (m, 1H), 1.15-1.07 (m, 1H), 0.95-0.87 (m, 1H), 0.71-0.66 (m, 1H), 0.31 (apparent q, J=6.0 Hz, 1H). the resulting solution was cooled in an ice bath the slurry was stirred for 15 min then poured onto petroleum ether The mixture was filtered repeatedly through CELITE until a transparent solution was obtained This mixture was concentrated at 100 mbar was further diluted with THF The mixture was cooled to 0° C. After 10 min to warm to 20° C. The aqueous phase was extracted with EtOAc the combined organic extracts were washed with brine then dried Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (1R,2R)-2-(pent-4-en-1-yl)cyclopropanol (See International Patent Application Publication No. WO08/057209) (2.13 g; 70% wt) in acetonitrile (20 ml) was added pyridine (1.5 ml), followed by N,N′-disuccinimidyl carbonate (3.74 g) and a crystal of DMAP. The mixture was stirred at 40° C. overnight. After cooling to room temperature, the reaction mixture was diluted with ether and washed with HCl 1N, water and brine and dried over sodium sulfate. The organic layer was filtered and concentrated to provide the desired product (2.88 g) as an oil. 1H NMR (500 MHz, CDCl3): δ (ppm) 4.06-4.03 (m, 1H), 2.87 (s, 4H), 2.28-2.25 (m, 2H), 1.98-1.97 (m, 1H), 1.72-1.65 (m, 2H), 1.46-1.40 (m, 2H), 1.31-1.24 (m, 1H), 1.12-1.08 (m, 1H), 0.72-0.68 (m, 1H). After cooling to room temperature washed with HCl 1N, water and brine dried over sodium sulfate The organic layer was filtered concentrated

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

Procedure: To a solution of (1R,2R)-2-(pent-4-en-1-yl)cyclopropanol (see International Patent Application Publication No. WO 08/057209) (17.1 g) in acetonitrile (193 mL) was added N,N′-disuccinimidyl carbonate (49.3 g) then triethylamine (53.7 mL) The mixture was heated to 40° C. for 18 hours. The reaction mixture was cooled to room temperature and the solids were removed by filtration. The solvent was removed in vacuo. The residue was purified by flash chromatography (ISCO, 10 to 70% ethyl acetate in hexanes) to give the desired product (18 g). 1H NMR (500 MHz, CDCl3): δ (ppm) 4.06-4.03 (m, 1H), 2.87 (s, 4H), 2.28-2.25 (m, 2H), 1.98-1.97 (m, 1H), 1.72-1.63 (m, 2H), 1.44-1.39 (m, 2H), 1.30-1.25 (m, 1H), 1.12-1.08 (m, 1H), 0.72-0.68 (m, 1H). the solids were removed by filtration The solvent was removed in vacuo The residue was purified by flash chromatography (ISCO, 10 to 70% ethyl acetate in hexanes)

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

Procedure: To a solution of (1R,2R)-2-(pent-4-en-1-yl)cyclopropanol (see International Patent Application Publication No. WO 08/057209) (17.1 g) in acetonitrile (193 mL) was added N,N′-disuccinimidyl carbonate (49.3 g) then triethylamine (53.7 mL) The mixture was heated to 40° C. for 18 hours. The reaction mixture was cooled to room temperature and the solids were removed by filtration. The solvent was removed in vacuo. The residue was purified by flash chromatography (ISCO, 10 to 70% ethyl acetate in hexanes) to give the desired product (18 g). 1H NMR (500 MHz, CDCl3): δ (ppm) 4.06-4.03 (m, 1H), 2.87 (s, 4H), 2.28-2.25 (m, 2H), 1.98-1.97 (m, 1H), 1.72-1.63 (m, 2H), 1.44-1.39 (m, 2H), 1.30-1.25 (m, 1H), 1.12-1.08 (m, 1H), 0.72-0.68 (m, 1H). the solids were removed by filtration The solvent was removed in vacuo The residue was purified by flash chromatography (ISCO, 10 to 70% ethyl acetate in hexanes)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution (0.45 M) of the preceding compound in hexane was treated with a solution (15%) of Et2Zn (1.2 eq) in toluene, and the resulting solution was cooled in an ice bath. Diiodomethane (1.2 eq) was added dropwise, then the solution was stirred for 1 h before being warmed to 20° C. Pyridine (6 eq) was added, and the slurry was stirred for 15 min then poured onto petroleum ether. The mixture was filtered repeatedly through CELITE until a transparent solution was obtained. This mixture was concentrated at 100 mbar, and the solution that remained (that contained trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane, toluene and pyridine) was further diluted with THF. The mixture was cooled to 0° C. then treated dropwise with a solution (1 M) of TBAF (1.2 eq) in THF. After 10 min, the mixture was allowed to warm to 20° C., and after a further 1 h was poured into H2O. The aqueous phase was extracted with EtOAc, and the combined organic extracts were washed with brine then dried. Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether) to furnish the title compound (71%) as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.85-5.75 (m, 1H), 5.00 (dd, J=17.1, 1.6 Hz, 1H), 4.94 (br d, J=10.4 Hz, 1H), 3.20 (apparent dt, J=6.4, 2.5 Hz, 1H), 2.10-2.04 (m, 2H), 1.52-1.44 (m, 2H), 1.29-1.19 (m, 1H), 1.15-1.07 (m, 1H), 0.95-0.87 (m, 1H), 0.71-0.66 (m,1H), 0.31 (apparent q, J=6.0 Hz, 1H). the resulting solution was cooled in an ice bath the slurry was stirred for 15 min then poured onto petroleum ether The mixture was filtered repeatedly through CELITE until a transparent solution was obtained This mixture was concentrated at 100 mbar was further diluted with THF The mixture was cooled to 0° C. After 10 min to warm to 20° C. The aqueous phase was extracted with EtOAc the combined organic extracts were washed with brine then dried Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution (0.45 M) of the preceding compound in hexane was treated with a solution (15%) of Et2Zn (1.2 eq) in toluene, and the resulting solution was cooled in an ice bath. Diiodomethane (1.2 eq) was added dropwise, then the solution was stirred for 1 h before being warmed to 20° C. Pyridine (6 eq) was added, and the slurry was stirred for 15 min then poured onto petroleum ether. The mixture was filtered repeatedly through CELITE until a transparent solution was obtained. This mixture was concentrated at 100 mbar, and the solution that remained (that contained trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane, toluene and pyridine) was further diluted with THF. The mixture was cooled to 0° C. then treated dropwise with a solution (1 M) of TBAF (1.2 eq) in THF. After 10 min, the mixture was allowed to warm to 20° C., and after a further 1 h was poured into H2O. The aqueous phase was extracted with EtOAc, and the combined organic extracts were washed with brine then dried. Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether) to furnish the title compound (71%) as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.85-5.75 (m, 1H), 5.00 (dd, J=17.1, 1.6 Hz, 1H), 4.94 (br d, J=10.4 Hz, 1H), 3.20 (apparent dt, J=6.4, 2.5 Hz, 1H), 2.10-2.04 (m, 2H), 1.52-1.44 (m, 2H), 1.29-1.19 (m, 1H), 1.15-1.07 (m, 1H), 0.95-0.87 (m, 1H), 0.71-0.66 (m, 1H), 0.31 (apparent q, J=6.0 Hz, 1H). the resulting solution was cooled in an ice bath the slurry was stirred for 15 min then poured onto petroleum ether The mixture was filtered repeatedly through CELITE until a transparent solution was obtained This mixture was concentrated at 100 mbar was further diluted with THF The mixture was cooled to 0° C. After 10 min to warm to 20° C. The aqueous phase was extracted with EtOAc the combined organic extracts were washed with brine then dried Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (1R,2R)-2-(pent-4-en-1-yl)cyclopropanol (See International Patent Application Publication No. WO08/057209) (2.13 g; 70% wt) in acetonitrile (20 ml) was added pyridine (1.5 ml), followed by N,N′-disuccinimidyl carbonate (3.74 g) and a crystal of DMAP. The mixture was stirred at 40° C. overnight. After cooling to room temperature, the reaction mixture was diluted with ether and washed with HCl 1N, water and brine and dried over sodium sulfate. The organic layer was filtered and concentrated to provide the desired product (2.88 g) as an oil. 1H NMR (500 MHz, CDCl3): δ (ppm) 4.06-4.03 (m, 1H), 2.87 (s, 4H), 2.28-2.25 (m, 2H), 1.98-1.97 (m, 1H), 1.72-1.65 (m, 2H), 1.46-1.40 (m, 2H), 1.31-1.24 (m, 1H), 1.12-1.08 (m, 1H), 0.72-0.68 (m, 1H). After cooling to room temperature washed with HCl 1N, water and brine dried over sodium sulfate The organic layer was filtered concentrated

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

Procedure: To a solution of (1R,2R)-2-(pent-4-en-1-yl)cyclopropanol (see International Patent Application Publication No. WO 08/057209) (17.1 g) in acetonitrile (193 mL) was added N,N′-disuccinimidyl carbonate (49.3 g) then triethylamine (53.7 mL) The mixture was heated to 40° C. for 18 hours. The reaction mixture was cooled to room temperature and the solids were removed by filtration. The solvent was removed in vacuo. The residue was purified by flash chromatography (ISCO, 10 to 70% ethyl acetate in hexanes) to give the desired product (18 g). 1H NMR (500 MHz, CDCl3): δ (ppm) 4.06-4.03 (m, 1H), 2.87 (s, 4H), 2.28-2.25 (m, 2H), 1.98-1.97 (m, 1H), 1.72-1.63 (m, 2H), 1.44-1.39 (m, 2H), 1.30-1.25 (m, 1H), 1.12-1.08 (m, 1H), 0.72-0.68 (m, 1H). the solids were removed by filtration The solvent was removed in vacuo The residue was purified by flash chromatography (ISCO, 10 to 70% ethyl acetate in hexanes)