(2S,3S)-3-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoic acid

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 39.3 g Boc-MeIle-OH (0.160 mol; Synthetech) were dissolved in 160 ml THF and cooled to 0° C. 240 ml 1M BH3-THF (0.24 mol; Fluka) were added at 0° C. over 1 h and the clear, colorless reaction mixture was warmed up and stirred at RT for 1 h. The reaction mixture was again cooled to 0° C., 100 ml deionized water were carefully added at 0-5° C. over 0.5 h and after warming up to RT stirring was continued for 1 h. To the colorless solution were added 250 ml 10% Na2CO3 all at once and after stirring for 1 h the reaction mixture was extracted with 1000 ml and 500 ml ethyl acetate. The organic layers were washed with brine and dried (Na2SO4). Removal of the solvent by rotary evaporation gave 36.9 g (99.7%) product as colorless oil. the clear, colorless reaction mixture was warmed up The reaction mixture was again cooled to 0° C. were carefully added at 0-5° C. over 0.5 h after warming up to RT stirring was continued for 1 h after stirring for 1 h the reaction mixture was extracted with 1000 ml and 500 ml ethyl acetate The organic layers were washed with brine dried (Na2SO4) Removal of the solvent by rotary evaporation

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 39.3 g Boc-MeIle-OH (0.160 mol; Synthetech) were dissolved in 160 ml THF and cooled to 0° C. 240 ml 1M BH3-THF (0.24 mol; Fluka) were added at 0° C. over 1 h and the clear, colorless reaction mixture was warmed up and stirred at RT for 1 h. The reaction mixture was again cooled to 0° C., 100 ml deionized water were carefully added at 0-5° C. over 0.5 h and after warming up to RT stirring was continued for 1 h. To the colorless solution were added 250 ml 10% Na2CO3 all at once and after stirring for 1 h the reaction mixture was extracted with 1000 ml and 500 ml ethyl acetate. The organic layers were washed with brine and dried (Na2SO4). Removal of the solvent by rotary evaporation gave 36.9 g (99.7%) product as colorless oil. the clear, colorless reaction mixture was warmed up The reaction mixture was again cooled to 0° C. were carefully added at 0-5° C. over 0.5 h after warming up to RT stirring was continued for 1 h after stirring for 1 h the reaction mixture was extracted with 1000 ml and 500 ml ethyl acetate The organic layers were washed with brine dried (Na2SO4) Removal of the solvent by rotary evaporation

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

実験手順: Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester and (2S,3S)-2-(tert-butoxycarbonyl-methyl-amino)-3-methyl-pentanoic acid to yield (3aR,4S,7aR)-4-[(2S,3S)-2-(tert-butoxycarbonyl-methyl-amino)-3-methyl-pentanoyloxy]-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester. This NBoc-protected product was then stirred in hydrochloric acid dioxane solution (4M, 10 equiv.) at room temperature for 6 hrs. Subsequently the solvent was removed the residue dissolved in dichloromethane and washed with saturated sodium hydrogencarbonate solution. The organic layer was tried with sodium sulfate, filtrated and evaporated. The crude product was subjected to silica gel flash chromatography (ISCO CombiFlash; dichloromethane/methanol; 100/0 to 95/5) to yield (3aR,4S,7aR)-4-((2S,3S)-3-methyl-2-methylamino-pentanoyloxy)-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester. MS [M+H] 296 (ester elimination ion); RT=5.213 min; HPLC Method I

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 39.3 g Boc-MeIle-OH (0.160 mol; Synthetech) were dissolved in 160 ml THF and cooled to 0° C. 240 ml 1M BH3-THF (0.24 mol; Fluka) were added at 0° C. over 1 h and the clear, colorless reaction mixture was warmed up and stirred at RT for 1 h. The reaction mixture was again cooled to 0° C., 100 ml deionized water were carefully added at 0-5° C. over 0.5 h and after warming up to RT stirring was continued for 1 h. To the colorless solution were added 250 ml 10% Na2CO3 all at once and after stirring for 1 h the reaction mixture was extracted with 1000 ml and 500 ml ethyl acetate. The organic layers were washed with brine and dried (Na2SO4). Removal of the solvent by rotary evaporation gave 36.9 g (99.7%) product as colorless oil. the clear, colorless reaction mixture was warmed up The reaction mixture was again cooled to 0° C. were carefully added at 0-5° C. over 0.5 h after warming up to RT stirring was continued for 1 h after stirring for 1 h the reaction mixture was extracted with 1000 ml and 500 ml ethyl acetate The organic layers were washed with brine dried (Na2SO4) Removal of the solvent by rotary evaporation