(S)-1-Benzyl 2-tert-butyl pyrrolidine-1,2-dicarboxylate

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

実験手順: Benzyloxycarbonyl-L-proline tert.butyl ester (205 g.) is dissolved in absolute ethanol (1.2 l) and hydrogenated at normal pressure with 10% Pd on carbon (10 g.) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm Hg. The residue is distilled in vacuo, to obtain L-proline tert.butyl ester, b.p.1mm 50°-51°. The catalyst is filtered off the filtrate is concentrated in vacuo at 30 mm Hg The residue is distilled in vacuo

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

実験手順: Benzyloxycarbonyl-L-proline tert.butyl ester (205 g.) is dissolved in absolute ethanol (1.2 l) and hydrogenated at normal pressure with 10% Pd on carbon (10 g.) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm Hg. The residue is distilled in vacuo, to obtain L-proline tert.butyl ester, b.p.1mm 50°-51°. The catalyst is filtered off the filtrate is concentrated in vacuo at 30 mm Hg The residue is distilled in vacuo

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

実験手順: The benzyloxycarbonyl-L-proline thus obtained (180 g.) is dissolved in a mixture of dichloromethane (300 ml.), liquid isobutylene (800 ml.) and concentrated sulfuric acid (7.2 ml.). The solution is shaken in a pressure bottle for 72 hours. The pressure is released, the isobutylene is allowed to evaporate and the solution is washed with 5% sodium carbonate, water, dried over magnesium sulfate and concentrated to dryness in vacuo, to obtain benzyloxycarbonyl-L-proline tert.butyl ester, yield 205 g. to evaporate the solution is washed with 5% sodium carbonate, water dried over magnesium sulfate concentrated to dryness in vacuo

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

実験手順: Benzyloxycarbonyl-L-proline tert.butyl ester (205 g.) is dissolved in absolute ethanol (1.2 l) and hydrogenated at normal pressure with 10% Pd on carbon (10 g.) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm. Hg. The residue is distilled in vacuo, to obtain L-proline tert.butyl ester, b.p.1mm 50°-51°. The catalyst is filtered off the filtrate is concentrated in vacuo at 30 mm. Hg The residue is distilled in vacuo

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

実験手順: Benzyloxycarbonyl-L-proline tert.butyl ester (205 g.) is dissolved in absolute ethanol (1.2 l) and hydrogenated at normal pressure with 10% Pd on carbon (10 g.) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm. Hg. The residue is distilled in vacuo, to obtain L-proline tert.butyl ester, b.p.1mm 50°-51°. The catalyst is filtered off the filtrate is concentrated in vacuo at 30 mm. Hg The residue is distilled in vacuo

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

実験手順: The benzyloxycarbonyl-L-proline thus obtained (180 g.) is dissolved in a mixture of dichloromethane (300 ml.), liquid isobutylene (800 ml.) and concentrated sulfuric acid (7.2 ml.). The solution is shaken in a pressure bottle for 72 hours. The pressure is released, the isobutylene is allowed to evaporate and the solution is washed with 5% sodium carbonate, water, dried over magnesium sulfate and concentrated to dryness in vacuo, to obtain benzyloxycarbonyl-L-proline tert.butyl ester, yield 205 g. to evaporate the solution is washed with 5% sodium carbonate, water dried over magnesium sulfate concentrated to dryness in vacuo

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

実験手順: The benzyloxycarbonyl-L-proline thus obtained (180 g.) is dissolved in a mixture of dichloromethane (300 ml.), liquid isobutylene (800 ml.) and concentrated sulfuric acid (7.2 ml.). The solution is shaken in a pressure bottle for 72 hours. The pressure is released, the isobutylene is allowed to evaporate and the solution is washed with 5% sodium carbonate, water, dried over magnesium sulfate and concentrated to dryness in vacuo, to obtain benzyloxycarbonyl-L-proline tert.butyl ester, yield 205 g. to evaporate the solution is washed with 5% sodium carbonate, water dried over magnesium sulfate concentrated to dryness in vacuo

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

実験手順: An ice-cooled (0° C.) stirred solution of (S)-proline tert-butyl ester (2) (24.5 g, 143 mmol) and anhydrous diisopropylethylamine (DIPEA) (32.4 mL, 186 mmol) in dry THF (400 mL) was treated with benzylchloroformate (24.6 mL, 172 mmol). After 5 min, the cooling bath and removed and the reaction mixture was stirred at room temperature for 6 h. The mixture was poured into ether (500 mL) and 1 N HCl (400 mL). The organic fraction was washed with H2O (200 mL) and brine (200 mL), and dried over MgSO4. The solvent was removed in vacuo and the resultant oil (43.0 g; 99% was used without further purification. A portion (1 g) was purified by flash chromatography (SiO2; 10% EtOAc in hexane, Rƒ0.25) yielding a clear colorless oil (990 mg): 1H NMR (200 MHz, CDCl3) δ 7.22-7.42 (m, 5H, Ar—H), 5.02-5.22 (m, 2H, OCH2), 4.18-4.20 (m, 1H, α-CH), 3.40-3.65 (m, 2H, δ-CH2), 2.10-2.24 (m, 1H), 1.80-2.10 (m, 3H), 1.35 & 1.43 (s, 9H, C(CH3)3). the cooling bath and removed The mixture was poured into ether (500 mL) and 1 N HCl (400 mL) The organic fraction was washed with H2O (200 mL) and brine (200 mL) dried over MgSO4 The solvent was removed in vacuo 99% was used without further purification A portion (1 g) was purified by flash chromatography (SiO2; 10% EtOAc in hexane, Rƒ0.25)

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

実験手順: Benzyloxycarbonyl-L-proline tert.butyl ester (205 g.) is dissolved in absolute ethanol (1.2 l) and hydrogenated at normal pressure with 10% Pd on carbon (10 g.) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm Hg. The residue is distilled in vacuo, to obtain L-proline tert.butyl ester, b.p.1mm 50°-51°. The catalyst is filtered off the filtrate is concentrated in vacuo at 30 mm Hg The residue is distilled in vacuo

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

実験手順: Benzyloxycarbonyl-L-proline tert.butyl ester (205 g.) is dissolved in absolute ethanol (1.2 l) and hydrogenated at normal pressure with 10% Pd on carbon (10 g.) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm Hg. The residue is distilled in vacuo, to obtain L-proline tert.butyl ester, b.p.1mm 50°-51°. The catalyst is filtered off the filtrate is concentrated in vacuo at 30 mm Hg The residue is distilled in vacuo

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

実験手順: The benzyloxycarbonyl-L-proline thus obtained (180 g.) is dissolved in a mixture of dichloromethane (300 ml.), liquid isobutylene (800 ml.) and concentrated sulfuric acid (7.2 ml.). The solution is shaken in a pressure bottle for 72 hours. The pressure is released, the isobutylene is allowed to evaporate and the solution is washed with 5% sodium carbonate, water, dried over magnesium sulfate and concentrated to dryness in vacuo, to obtain benzyloxycarbonyl-L-proline tert.butyl ester, yield 205 g. to evaporate the solution is washed with 5% sodium carbonate, water dried over magnesium sulfate concentrated to dryness in vacuo

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

実験手順: 9.15 g of Z-Pro-OtBu are hydrogenated in 100 ml of methanol and 1.0 g of Pd on charcoal (10%) at room temperature. The hydrogen uptake has ended after 30 minutes. The solution is freed of catalyst by filtration and evaporated in a waterpump vacuum at 30° C. The resulting oil is homogeneous in a thin layer chromatogram on silica gel. Rf = 0.55 in the system chloroform-methanol (1:1). at room temperature The solution is freed of catalyst by filtration evaporated in a waterpump vacuum at 30° C