Boron trifluoride etherate → 1-Benzyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate

HRID 2186684Notes

Reaction equation

HRID 2186684 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1.[CH2:18]([O:20][C:21](=[O:25])[CH:22]=[N+]=[N-])[CH3:19].B(F)(F)F.CCOCC>CCOCC>[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:9])[CH2:4][CH2:3][CH:22]1[C:21]([O:20][CH2:18][CH3:19])=[O:25]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 12192Ethyl diazoacetateHCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 146001211-Benzyl 4-ethyl 5-oxoazepane-1,4-dicarboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-45 °C

Procedure

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, 40% EtOAc/hexane), yielding product as pale yellow oil (42.1 g, 88%). 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.

Workup

  1. customwas kept below −25° C
  2. customquenched with sat. NaHCO3
  3. customThe ice bath was removed
  4. additionThe reaction was diluted with EtOAc (250 ml) and H2O (150 ml)
  5. customThe layers were separated
  6. dry with materialthe organic phase was dried over MgSO4
  7. concentrationIt was concentrated under reduced pressure to an orange oil
  8. customThe product was purified by flash chromatography (silica gel, 40% EtOAc/hexane)

Sources & evidence

ORD record
ord-1101a578e87c43a08f9f5c2c34b7b908
Source dataset
uspto-grants-2002_06
Patent number
US06407092B1

Reaction notes

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