tert-Butyl (3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl)carbamate

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

実験手順: A solution of tert-butyl[3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl]carbamate (8.3 g, 26.3 mmol) in EtOAc (130 mL) was heated at reflux for 4 h. The solution was concentrated to afford the title compound which was used without further purification. LRMS (ESI) m/z 214.2 [(M+H)+; calcd for C10H15NO4: 214]. at reflux for 4 h The solution was concentrated

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

実験手順: To a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (3.81 g, 26.4 mmol) in CH2Cl2 (34 mL) at 0° C. was added 3-[(tert-butoxycarbonyl)amino]propanoic acid (5.0 g, 26.4 mmol), DMAP (4.84 g, 39.6 mmol), and EDC (6.08 g, 31.7 mmol). The mixture was stirred at rt for 5 h. The resulting mixture was washed with 10% aq. KHSO4 (4×), dried (Na2SO4) and concentrated to afford the title compound which was used without further purification. LRMS (ESI) m/z 316.1 [(M+H)+; calcd for C14H21NO7: 316]. The resulting mixture was washed with 10% aq. KHSO4 (4×) dried (Na2SO4) concentrated

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

実験手順: To a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (3.81 g, 26.4 mmol) in CH2Cl2 (34 mL) at 0° C. was added 3-[(tert-butoxycarbonyl)amino]propanoic acid (5.0 g, 26.4 mmol), DMAP (4.84 g, 39.6 mmol), and EDC (6.08 g, 31.7 mmol). The mixture was stirred at rt for 5 h. The resulting mixture was washed with 10% aq. KHSO4 (4×), dried (Na2SO4) and concentrated to afford the title compound which was used without further purification. LRMS (ESI) m/z 316.1 [(M+H)+; calcd for C14H21NO7: 316]. The resulting mixture was washed with 10% aq. KHSO4 (4×) dried (Na2SO4) concentrated

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

実験手順: Boc-β-alanine (25 g, 132 mmol), Meldrum's acid (20.9 g, 145 mmol) and 4-dimethylaminopyridine (DMAP, 24.2 g, 198 mmol) were dissolved in 700 mL of dry dichloromethane (DCM) at 0° C. under nitrogen atmosphere. To this solution 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 30.4 g, 158 mmol) was added. The resulting solution was allowed to reach room temperature and stirred overnight. The reaction mixture was washed (0.5 L×4) with 5% KHSO4 aqueous solution. The organic layer was dried over anh. Na2SO4, filtered and evaporated under vacuum, affording crude [3-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-3-oxo-propyl]-carbamic acid tert-butyl ester that was dissolved in 600 mL of ethylacetate and refluxed for 4 hours. The solvent was reduced to 150 mL under vacuum and the resulting solution was allowed to crystallize at 4° C. overnight. The solid was filtered and washed with cold ethyl acetate affording 18.4 g (65% yield) of the title compound. to reach room temperature The reaction mixture was washed (0.5 L×4) with 5% KHSO4 aqueous solution The organic layer was dried over anh. Na2SO4 filtered evaporated under vacuum

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-butyl 3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropylcarbamate (I-59b: 50 g, 158.57 mmol) was dissolved in ethyl acetate (500 mL) at room temperature under nitrogen atmosphere and the resulting reaction mass was heated at 105° C. for 20 hours. The reaction was monitored by TLC (10% methanol in DCM). The reaction mass was cooled to room temperature and concentrated under reduced pressure to afford the crude product. Purification by ether-wash afforded 28 g of the product (83% yield). the resulting reaction mass The reaction mass was cooled to room temperature concentrated under reduced pressure to afford the crude product Purification by ether- wash

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

実験手順: EDCI (59.39 g, 310.8 mmol) was added at 0° C. to a stirred solution of 3-(tert-butoxycarbonylamino)propanoic acid (I-59a: 49 g, 258.9 mmol), meldrum's acid (41.05 g, 284.8 mmol) and DMAP (47.4 g, 388.5 mmol) in DCM (490 mL) and the resulting reaction mass was allowed to stir at room temperature overnight. The reaction was monitored by TLC (10% methanol in CHCl3). The reaction mass was washed with 5% KHSO4 solution and separated the layers. The organic layer was dried over Na2SO4 and concentrated to afford 70 g of the product (85.8% yield). the resulting reaction mass The reaction mass was washed with 5% KHSO4 solution separated the layers The organic layer was dried over Na2SO4 concentrated

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

実験手順: A solution of tert-butyl[3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-3-oxopropyl]carbamate (8.3 g, 26.3 mmol) in EtOAc (130 mL) was heated at reflux for 4 h. The solution was concentrated to afford the title compound which was used without further purification. LRMS (ESI) m/z 214.2 [(M+H)+; calcd for C10H15NO4: 214]. at reflux for 4 h The solution was concentrated

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

実験手順: To a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (3.81 g, 26.4 mmol) in CH2Cl2 (34 mL) at 0° C. was added 3-[(tert-butoxycarbonyl)amino]propanoic acid (5.0 g, 26.4 mmol), DMAP (4.84 g, 39.6 mmol), and EDC (6.08 g, 31.7 mmol). The mixture was stirred at rt for 5 h. The resulting mixture was washed with 10% aq. KHSO4 (4×), dried (Na2SO4) and concentrated to afford the title compound which was used without further purification. LRMS (ESI) m/z 316.1 [(M+H)+; calcd for C14H21NO7: 316]. The resulting mixture was washed with 10% aq. KHSO4 (4×) dried (Na2SO4) concentrated