methyl (2S)-2-isocyanato-3,3-dimethylbutanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution (0.39 M) of methyl 3-methyl-L-valinate in a 2:1 mixture of saturated aqueous NaHCO3 and CH2Cl2 was cooled in an ice bath and stirred rapidly. The mixture was treated with triphosgene (0.45 eq) in one portion, and the resulting mixture was stirred for 0.5 h. The reaction was diluted with CH2Cl2, and the layers were separated. The aqueous phase was extracted with CH2Cl2, then the combined organics were washed with brine and dried. Removal of the solvent gave the title compound as clear oil that was kept for 12 h under vacuum (0.1 mbar) then used directly in the subsequent step. 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.75 (s, 1H), 1.00 (s, 9H). was cooled in an ice bath the resulting mixture was stirred for 0.5 h the layers were separated The aqueous phase was extracted with CH2Cl2 the combined organics were washed with brine dried Removal of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution (0.39 M) of methyl 3-methyl-L-valinate in a 2:1 mixture of saturated aqueous NaHCO3 and CH2Cl2 was cooled in an ice bath and stirred rapidly. The mixture was treated with triphosgene (0.45 eq) in one portion, and the resulting mixture was stirred for 0.5 h. The reaction was diluted with CH2Cl2, and the layers were separated. The aqueous phase was extracted with CH2Cl2, then the combined organics were washed with brine and dried. Removal of the solvent gave the title compound as clear oil that was kept for 12 h under vacuum (0.1 mbar) then used directly in the subsequent step. 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.75 (s, 1H), 1.00 (s, 9H). was cooled in an ice bath the resulting mixture was stirred for 0.5 h the layers were separated The aqueous phase was extracted with CH2Cl2 the combined organics were washed with brine dried Removal of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution (0.39 M) of methyl 3-methyl-L-valinate in a 2:1 mixture of saturated aqueous NaHCO3 and CH2Cl2 was cooled in an ice bath and stirred rapidly. The mixture was treated with triphosgene (0.45 eq) in one portion, and the resulting mixture was stirred for 0.5 h. The reaction was diluted with CH2Cl2, and the layers were separated. The aqueous phase was extracted with CH2Cl2, then the combined organics were washed with brine and dried. Removal of the solvent gave the title compound as clear oil that was kept for 12 h under vacuum (0.1 mbar) then used directly in the subsequent step. 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.75 (s, 1H), 1.00 (s, 9H). was cooled in an ice bath the resulting mixture was stirred for 0.5 h the layers were separated The aqueous phase was extracted with CH2Cl2 the combined organics were washed with brine dried Removal of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution (0.39 M) of methyl 3-methyl-L-valinate in a 2:1 mixture of saturated aqueous NaHCO3 and CH2Cl2 was cooled in an ice bath and stirred rapidly. The mixture was treated with triphosgene (0.45 eq) in one portion, and the resulting mixture was stirred for 0.5 h. The reaction was diluted with CH2Cl2, and the layers were separated. The aqueous phase was extracted with CH2Cl2, then the combined organics were washed with brine and dried. Removal of the solvent gave the title compound as clear oil that was kept for 12 h under vacuum (0.1 mbar) then used directly in the subsequent step. 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.75 (s, 1H), 1.00 (s, 9H). was cooled in an ice bath the resulting mixture was stirred for 0.5 h the layers were separated The aqueous phase was extracted with CH2Cl2 the combined organics were washed with brine dried Removal of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-methylpent-4-en-l-amine (2.0 g, 20.2 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature under nitrogen. To this was added methyl 3-methyl-N-(oxomethylene)-L-valinate (3.5 g, 20.2 mmol) and the resulting solution stirred 2 h. Contents of the reaction flask were evaporated and subjected to flash column chromatography eluting with hexane/ethyl acetate 60/40 to give methyl 3-Methyl-N-{[methyl(pent-4-enyl)amino]carbonyl}-L-valinate as an orange oil, 3.02 g (55% yield). Contents of the reaction flask were evaporated eluting with hexane/ethyl acetate 60/40

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-methylpent-4-en-l-amine (2.0 g, 20.2 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature under nitrogen. To this was added methyl 3-methyl-N-(oxomethylene)-L-valinate (3.5 g, 20.2 mmol) and the resulting solution stirred 2 h. Contents of the reaction flask were evaporated and subjected to flash column chromatography eluting with hexane/ethyl acetate 60/40 to give methyl 3-Methyl-N-{[methyl(pent-4-enyl)amino]carbonyl}-L-valinate as an orange oil, 3.02 g (55% yield). Contents of the reaction flask were evaporated eluting with hexane/ethyl acetate 60/40

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl 3-methyl-L-valinate hydrochloride (10.0 g, 54.9 mmol) and pyridine (22.3 mL, 276 mmol) in methylenechloride (300 mL) was cooled in an ice bath under nitrogen. Phosgene (20% in toluene, 41.1 mL, 83.0 mmol) was added dropwise over 0.5 h using an addition funnel. The resulting mixture was stirred 1 h then poured into cold 1M hydrochloric acid and extracted with methylenechloride (3×100 mL). The combined organic extracts were washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated. Flash column chromatography eluting with hexane/ethyl acetate 90/10 gave methyl 3-methyl-N-(oxomethylene)-L-valinate as an orange oil, 6.99 g (74% yield). extracted with methylenechloride (3×100 mL) The combined organic extracts were washed with brine dried with anhydrous magnesium sulfate filtered concentrated Flash column chromatography eluting with hexane/ethyl acetate 90/10

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl 3-methyl-L-valinate hydrochloride (10.0 g, 54.9 mmol) and pyridine (22.3 mL, 276 mmol) in methylenechloride (300 mL) was cooled in an ice bath under nitrogen. Phosgene (20% in toluene, 41.1 mL, 83.0 mmol) was added dropwise over 0.5 h using an addition funnel. The resulting mixture was stirred 1 h then poured into cold 1M hydrochloric acid and extracted with methylenechloride (3×100 mL). The combined organic extracts were washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated. Flash column chromatography eluting with hexane/ethyl acetate 90/10 gave methyl 3-methyl-N-(oxomethylene)-L-valinate as an orange oil, 6.99 g (74% yield). extracted with methylenechloride (3×100 mL) The combined organic extracts were washed with brine dried with anhydrous magnesium sulfate filtered concentrated Flash column chromatography eluting with hexane/ethyl acetate 90/10

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-methylpent-4-en-1-amine (2.0 g, 20.2 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature under nitrogen. To this was added methyl 3-methyl-N-(oxomethylene)-L-valinate (3.5 g, 20.2 mmol) and the resulting solution stirred 2 h. Contents of the reaction flask were evaporated and subjected to flash column chromatography eluting with hexane/ethyl acetate 60/40 to give methyl 3-Methyl-N-{[methyl(pent-4-enyl)amino]carbonyl}-L-valinate as an orange oil, 3.02 g (55% yield). Contents of the reaction flask were evaporated eluting with hexane/ethyl acetate 60/40

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-methylpent-4-en-1-amine (ref: Org. Biomol. Chem.; EN; 2; 20; 2004; 3006-3017) (2.0 g, 21.2 mmol) in THF (20 mL) was added methyl 3-methyl-N-(oxomethylene)-L-valinate (Ref: EP 0 486 948 A2) (3.5 g, 20.2 mmol). After 2 h, the solvent was removed in vacuo and the crude material was purified on silica (40% EtOAc/hexanes) to yield the title compound. LRMS (M+H)+ 271.3 the solvent was removed in vacuo the crude material was purified on silica (40% EtOAc/hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution (0.39 M) of methyl 3-methyl-L-valinate in a 2:1 mixture of saturated aqueous NaHCO3 and CH2Cl2 was cooled in an ice bath and stirred rapidly. The mixture was treated with triphosgene (0.45 eq) in one portion, and the resulting mixture was stirred for 0.5 h. The reaction was diluted with CH2Cl2, and the layers were separated. The aqueous phase was extracted with CH2Cl2, then the combined organics were washed with brine and dried. Removal of the solvent gave the title compound as clear oil that was kept for 12 h under vacuum (0.1 mbar) then used directly in the subsequent step. 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.75 (s, 1H), 1.00 (s, 9H). was cooled in an ice bath the resulting mixture was stirred for 0.5 h the layers were separated The aqueous phase was extracted with CH2Cl2 the combined organics were washed with brine dried Removal of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution (0.39 M) of methyl 3-methyl-L-valinate in a 2:1 mixture of saturated aqueous NaHCO3 and CH2Cl2 was cooled in an ice bath and stirred rapidly. The mixture was treated with triphosgene (0.45 eq) in one portion, and the resulting mixture was stirred for 0.5 h. The reaction was diluted with CH2Cl2, and the layers were separated. The aqueous phase was extracted with CH2Cl2, then the combined organics were washed with brine and dried. Removal of the solvent gave the title compound as clear oil that was kept for 12 h under vacuum (0.1 mbar) then used directly in the subsequent step. 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.75 (s, 1H), 1.00 (s, 9H). was cooled in an ice bath the resulting mixture was stirred for 0.5 h the layers were separated The aqueous phase was extracted with CH2Cl2 the combined organics were washed with brine dried Removal of the solvent