tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate

Uses

tert-Butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate is a reagent used for the preparation of γ-butyrolactone derivative via Baeyer-Villiger monooxygenase (BVMO)-catalyzed oxidation.

Synthesis

A solution of crude tert-butyl 6-hydroxy-2-azaspiro[3.3]heptane-2-carboxylate (1.00 g,4.69mmol, 1.00 equiv) in dichloromethane(20 mL) was treated with Dess-Martin periodinane(2.10g,4.95 mmol, 1.06 equiv) in two batches a few min apart at 0 °C. After 10 min, the ice bath wasremoved, and the reaction was monitored by TLC (50% ethyl acetate, PMA stain). After 30 min.the reaction was diluted with ethyl acetate and washed twice with satd sodium bicarbonate. Theorganic layer was dried over sodium sulfate, filtered, and concentrated. The crude product waspurified by flash chromatography (80g silica gel, 10 to 50% ethyl acetate/heptane; pure fractionswere identified by TLC with PMA stain; an unidentified impurity elutes slightly earlier than theproduct) to give tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate as a white solid (721 mg,73%). mp 114.5-116C. 

References

[1] Patent: CN106565706, 2017, A. Location in patent: Paragraph 0176; 0177; 0178
[2] Organic Letters, 2009, vol. 11, # 16, p. 3523 - 3525
[3] Patent: US2011/319381, 2011, A1. Location in patent: Page/Page column 15
[4] Patent: US2012/129830, 2012, A1. Location in patent: Page/Page column 13
[5] Patent: WO2015/48507, 2015, A1. Location in patent: Paragraph 0219