N-BOC-HEXAHYDRO-5-OXOCYCLOPENTA[C]PYRROLE

Synthesis

General procedure for the synthesis of N-BOC-hexahydro-5-oxocyclopenta[C]pyrrole from tert-butyl 2-propenyl-2-propargylcarbamate: Compound 2B (39 g, 202.2 mmol) was dissolved in ethylene glycol dimethyl ether (275 mL), followed by the addition of octacyclohexane (83 g, 242.7 mmol) and water (82.4 mL). The reaction mixture was stirred for 30 minutes, then warmed to 84 °C and stirred continuously at this temperature for 16 hours. Upon completion of the reaction, the reaction solution was concentrated and saturated saline (500 mL), ethyl acetate (250 mL) and 1 mol/L hydrochloric acid (240 mL) were added to dissolve the residual solids. The aqueous phase was separated and extracted with ethyl acetate (250 mL x 3). All organic phases were combined, washed with saturated saline (250 mL x 2), and then dried over anhydrous sodium sulfate. After filtration, the organic phase was concentrated under reduced pressure and finally purified by silica gel column chromatography with an eluent ratio of petroleum ether/ethyl acetate (v/v) = 3:1 to 2:1 to obtain the target product 2C (27.6 g, 61.3% yield) as a light yellow solid.

References

[1] Patent: TW2017/8224, 2017, A. Location in patent: Page/Page column 33; 34
[2] Tetrahedron, 1993, vol. 49, # 23, p. 5047 - 5054
[3] Tetrahedron Letters, 1993, vol. 34, # 13, p. 2087 - 2090