Ethyl 1-Cbz-5-oxoazepane-4-carboxylate

To a suspension of benzyl 4-oxo-l-piperazinecarboxylate (11.7 g, 50.3 mmol) in diethyl ether (100 ml) at -78 Step l : 1-Benzyl 4-ethyl 5-oxoazepane-l, 4-dicarboxylate. To a solution of N-benzyloxycarbonyl-4-piperidone (1.27 mL, 6.5 mmol) in ether (15 mL) at -40°C was added boron trifluoride etherate (0.98 mL, 7.75 mmol) dropwise under nitrogen followed by dropwise addition of a solution of ethyl diazoacetate (0.80 mL, 7.75 mmol) in ether (5 mL) over 15 minutes. After 1 hour, the reaction was poured into ice/saturated sodium bicarbonate. The organic phase was collected, washed with brine, dried over sodium sulfate, and concentrated under vacuum to afford the title compound as a yellow oil (2.05 g, 99percent). The crude product was used without purification in the next step.A dry 500 ml 3-neck flask was charged with benzyl 4-oxo-1-piperidinecarboxylate (35.08 g, 150 mmol). It was dissolved in 130 ml Et2O and cooled to -45°C. Ethyldiazoacetate (20.5 ml, 195 mmol) and boron trifluoride ethyl ether (19.4 ml, 158 mmol) were added simultaneously by syringe pump over 45 minutes. The temperature was kept below -25°C. The reaction was stirred for 30 minutes longer, and then quenched with sat. NaHCO3. The ice bath was removed. The reaction was diluted with EtOAc (250 ml) and H2O (150 ml). The layers were separated, and the organic phase was dried over MgSO4. It was concentrated under reduced pressure to an orange oil. The product was purified by flash chromatography (silica gel, 40percent EtOAc/hexane), yielding product as pale yellow oil (42.1 g, 88percent). 1H NMR (CDCl3) δ 7.39-7.31, 5.15-5.12, 4.42-4.17, 3.96-3.83, 3.75-3.70, 3.65, 3.54-3.37, 2.08-2.03, 1.29-1.24; IR (liq.) 1743, 1702, 1476, 1455, 1443, 1425, 1371, 1318, 1295, 1238, 1213, 1178, 1098, 1068, 1028 cm -1.A dry 500 ml 3-neck flask was charged with benzyl 4-oxo-1-piperidinecarboxylate (35.08 g, 150 mmol). It was dissolved in 130 ml Et2O and cooled to -45°C. Ethyldiazoacetate (20.5 ml, 195 mmol) and boron trifluoride ethyl ether (19.4 ml, 158 mmol) were added simultaneously by syringe pump over 45 minutes. The temperature was kept below -25°C. The reaction was stirred for 30 minutes longer, and then quenched with sat. NaHCO3. The ice bath was removed. The reaction was diluted with EtOAc (250 ml) and H2O (150 ml). The layers were separated, and the organic phase was dried over MgSO4. It was concentrated under reduced pressure to an orange oil. The product was purified by flash chromatography (silica gel, 40percent EtOAc/hexane), yielding product as pale yellow oil (42.1 g, 88percent). 1H NMR (CDCl3) δ 7.39-7.31, 5.15-5.12, 4.42-4.17, 3.96-3.83, 3.75-3.70, 3.65, 3.54-3.37, 2.08-2.03, 1.29-1.24; IR (liq.) 1743, 1702, 1476, 1455, 1443, 1425, 1371, 1318, 1295, 1238, 1213, 1178, 1098, 1068, 1028 cm -1.To 1.0 g (4.28 mmol) 4-oxo-piperidine-1-carboxylic acid benzyl ester in 5 ml. anhydrous ether maintained between -25 °C and -30 °C were added, over 20 minutes, solutions of 0.7 ml. (5.56 mmol) BF2.12 Preparation of Compound 2 To a solution of compound 1 (15.0 g, 64.5 mmol) in THF (130 mL) was added NTo a solution of Compound 1 (8.0 g, 34.3 mmol) and ethyl 2-diazoacetate (5.1 g, 44.7 mmol) in THF (160 mL) was added BFTo a solution of Compound 1 (8.0 g, 34.3 mmol) and ethyl 2-diazoacetate (5.1 g, 44.7 mmol) in THF (160 mL) was added BFReaction Step 1

Molecular Weight:319.4
XLogP3:1.9
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:6
Exact Mass:319.14197277
Monoisotopic Mass:319.14197277
Topological Polar Surface Area:72.9
Heavy Atom Count:23
Complexity:431
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes