1-Oxa-5-azaspiro[2.4]heptane-5-carboxylic acid, 1,1-dimethylethyl ester

Uses

tert-butyl 1-oxa-5-azaspiro[2.4]heptane-5-carboxylate is ureful reactant for the synthesis of spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives.

Synthesis

At room temperature, tert-butyl 3-methylene pyrrolidine-1-carboxylate (195 mg, 1.06 mmol) was dissolved in dichloromethane (5 mL), followed by the addition of m-chloroperoxybenzoic acid (mCPBA, 275 mg, 1.60 mmol). The reaction mixture was stirred at room temperature for 4 hours. Upon completion of the reaction, the reaction was quenched with saturated sodium bicarbonate solution (2 mL) and then the organic phase was extracted with ethyl acetate (60 mL). The organic phase was washed sequentially with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting crude product was purified by fast silica gel column chromatography with the eluent being a hexane solution of 25% ethyl acetate to afford tert-butyl 1-oxa-5-azaspiro[2.4]heptane-5-carboxylate (150 mg, 0.753 mmol, 71% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 3.91-3.42 (m, 3H), 3.48-3.16 (m, 1H), 2.93 (s, 2H), 2.35-2.17 (m, 1H), 1.93-1.79 (m, 1H), 1.47 (s, 9H).

References

[1] Journal of Medicinal Chemistry, 2018, vol. 61, # 21, p. 9738 - 9755
[2] Patent: WO2015/35278, 2015, A1. Location in patent: Page/Page column 89
[3] Patent: US2017/233339, 2017, A1