(E)-hex-4-en-1-ol

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

Procedure: To a vessel maintained at 40° C. was charged CDI (2.75 g, 0.95 eq) and TBME (9 mL). To this mixture was added with stirring a solution of N-(t-butoxycarbonyl)glycine (3.1 g, 1.0 eq) dissolved in TBME (12 mL) over 30 min. Stirring was continued for an additional 30 min, whereupon trans-4-hexen-1-ol (1.7 g, 0.95 eq) was added over 30 min. The mixture was maintained with stirring at 40° C. for an additional 3.5 h, then cooled to ambient temperature and stirred a further 14 h. The mixture was washed with 1N HCl (2×7.8 mL) then water (1×7.8 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give (E)-hex-4-en-1-yl2-((tert-butoxycarbonyl)amino)acetate as an oil. The oil was dissolved in DCM (12 mL) and 4.0 M HCl in dioxane (2.8 mL) was added drop-wise. The mixture was stirred at ambient temperature for 1.5 h then the mixture was heated to 35° C. and stirred for 3 h. 4.0 M HCl in dioxane (2.8 mL) was added drop-wise. After 6 h at 35° C. a further dose of 4.0 M HCl in dioxane (2.8 mL) was added drop-wise and the mixture was stirred for a further 4 h. The mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. A portion of the residue (1.0 g) was dissolved in DCM (8 mL) and methyl 2-chloro-2-oxoacetate (0.63 g) was added. Triethylamine (1.0 g) was added drop-wise over 20 min. The mixture was stirred for 1 h before being quenched by 1N HCl (2.5 mL) to form a biphasic mixture. The layers were separated and the organic layer was washed with 1N HCl (1×2.5 mL), water (1×2.5 mL) and concentrated under reduced pressure to provide an oil. Flash column chromatography (SiO2, 10→60% EtOAc/Hex gradient) provided the title compound as an oil as a 95:5 mixture of trans:cis isomers. 1H NMR (300 MHz, CDCl3) δ ppm 7.57 (s, 1H), 5.31-5.55 (m, 2H), 4.17 (t, J=6.69 Hz, 2H), 4.12 (d, J=5.51 Hz, 2H), 3.92 (s, 3H), 1.97-2.10 (m, 2H), 1.67-1.77 (m, 2H), 1.62-1.67 (m, 3H); 13C NMR (75 MHz, CDCl3) δ ppm 168.60, 160.35, 156.28, 129.49, 126.12, 65.34, 53.68, 41.47, 28.62, 28.17, 17.84; HRMS (M+H) m/z, calcd for C11H18NO5, 244.1185; found 244.1187. To this mixture was added was added over 30 min The mixture was maintained with stirring at 40° C. for an additional 3.5 h cooled to ambient temperature stirred a further 14 h The mixture was washed with 1N HCl (2×7.8 mL) The organic layer was dried over Na2SO4 filtered concentrated

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

Procedure: To a vessel maintained at 40° C. was charged CDI (2.75 g, 0.95 eq) and TBME (9 mL). To this mixture was added with stirring a solution of N-(t-butoxycarbonyl)glycine (3.1 g, 1.0 eq) dissolved in TBME (12 mL) over 30 min. Stirring was continued for an additional 30 min, whereupon trans-4-hexen-1-ol (1.7 g, 0.95 eq) was added over 30 min. The mixture was maintained with stirring at 40° C. for an additional 3.5 h, then cooled to ambient temperature and stirred a further 14 h. The mixture was washed with 1N HCl (2×7.8 mL) then water (1×7.8 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give (E)-hex-4-en-1-yl2-((tert-butoxycarbonyl)amino)acetate as an oil. The oil was dissolved in DCM (12 mL) and 4.0 M HCl in dioxane (2.8 mL) was added drop-wise. The mixture was stirred at ambient temperature for 1.5 h then the mixture was heated to 35° C. and stirred for 3 h. 4.0 M HCl in dioxane (2.8 mL) was added drop-wise. After 6 h at 35° C. a further dose of 4.0 M HCl in dioxane (2.8 mL) was added drop-wise and the mixture was stirred for a further 4 h. The mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. A portion of the residue (1.0 g) was dissolved in DCM (8 mL) and methyl 2-chloro-2-oxoacetate (0.63 g) was added. Triethylamine (1.0 g) was added drop-wise over 20 min. The mixture was stirred for 1 h before being quenched by 1N HCl (2.5 mL) to form a biphasic mixture. The layers were separated and the organic layer was washed with 1N HCl (1×2.5 mL), water (1×2.5 mL) and concentrated under reduced pressure to provide an oil. Flash column chromatography (SiO2, 10→60% EtOAc/Hex gradient) provided the title compound as an oil as a 95:5 mixture of trans:cis isomers. 1H NMR (300 MHz, CDCl3) δ ppm 7.57 (s, 1H), 5.31-5.55 (m, 2H), 4.17 (t, J=6.69 Hz, 2H), 4.12 (d, J=5.51 Hz, 2H), 3.92 (s, 3H), 1.97-2.10 (m, 2H), 1.67-1.77 (m, 2H), 1.62-1.67 (m, 3H); 13C NMR (75 MHz, CDCl3) δ ppm 168.60, 160.35, 156.28, 129.49, 126.12, 65.34, 53.68, 41.47, 28.62, 28.17, 17.84; HRMS (M+H) m/z, calcd for C11H18NO5, 244.1185; found 244.1187. To this mixture was added was added over 30 min The mixture was maintained with stirring at 40° C. for an additional 3.5 h cooled to ambient temperature stirred a further 14 h The mixture was washed with 1N HCl (2×7.8 mL) The organic layer was dried over Na2SO4 filtered concentrated

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

Procedure: To a vessel maintained at 40° C. was charged CDI (2.75 g, 0.95 eq) and TBME (9 mL). To this mixture was added with stirring a solution of N-(t-butoxycarbonyl)glycine (3.1 g, 1.0 eq) dissolved in TBME (12 mL) over 30 min. Stirring was continued for an additional 30 min, whereupon trans-4-hexen-1-ol (1.7 g, 0.95 eq) was added over 30 min. The mixture was maintained with stirring at 40° C. for an additional 3.5 h, then cooled to ambient temperature and stirred a further 14 h. The mixture was washed with 1N HCl (2×7.8 mL) then water (1×7.8 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give (E)-hex-4-en-1-yl2-((tert-butoxycarbonyl)amino)acetate as an oil. The oil was dissolved in DCM (12 mL) and 4.0 M HCl in dioxane (2.8 mL) was added drop-wise. The mixture was stirred at ambient temperature for 1.5 h then the mixture was heated to 35° C. and stirred for 3 h. 4.0 M HCl in dioxane (2.8 mL) was added drop-wise. After 6 h at 35° C. a further dose of 4.0 M HCl in dioxane (2.8 mL) was added drop-wise and the mixture was stirred for a further 4 h. The mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. A portion of the residue (1.0 g) was dissolved in DCM (8 mL) and methyl 2-chloro-2-oxoacetate (0.63 g) was added. Triethylamine (1.0 g) was added drop-wise over 20 min. The mixture was stirred for 1 h before being quenched by 1N HCl (2.5 mL) to form a biphasic mixture. The layers were separated and the organic layer was washed with 1N HCl (1×2.5 mL), water (1×2.5 mL) and concentrated under reduced pressure to provide an oil. Flash column chromatography (SiO2, 10→60% EtOAc/Hex gradient) provided the title compound as an oil as a 95:5 mixture of trans:cis isomers. 1H NMR (300 MHz, CDCl3) δ ppm 7.57 (s, 1H), 5.31-5.55 (m, 2H), 4.17 (t, J=6.69 Hz, 2H), 4.12 (d, J=5.51 Hz, 2H), 3.92 (s, 3H), 1.97-2.10 (m, 2H), 1.67-1.77 (m, 2H), 1.62-1.67 (m, 3H); 13C NMR (75 MHz, CDCl3) δ ppm 168.60, 160.35, 156.28, 129.49, 126.12, 65.34, 53.68, 41.47, 28.62, 28.17, 17.84; HRMS (M+H) m/z, calcd for C11H18NO5, 244.1185; found 244.1187. To this mixture was added was added over 30 min The mixture was maintained with stirring at 40° C. for an additional 3.5 h cooled to ambient temperature stirred a further 14 h The mixture was washed with 1N HCl (2×7.8 mL) The organic layer was dried over Na2SO4 filtered concentrated