tert-Butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate

Uses

tert-Butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate is a useful research chemical.

Synthesis

General procedure for the synthesis of tert-butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate from 2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)acetic acid: to a stirred toluene (50 mL) at room temperature of 2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)acetic acid (2.1 g, 8.10 mmol) Triethylamine (TEA, 884 mg, 8.75 mmol) and diphenylphosphoryl azide (DPPA, 3 g, 10.94 mmol) were added to the solution. The reaction mixture was heated to 110 °C and stirred for 12 hours. The progress of the reaction was monitored by thin-layer chromatography (TLC); upon completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with dichloromethane (CH2Cl2, 2 × 20 mL). The combined organic extracts were dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel fast column chromatography, eluting with ethyl acetate (EtOAc) to afford tert-butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate (1.3 g, 63%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ 7.50 (s, 1H), 3.55-3.51 (m 2H), 3.30-3.23 (m, 4H), 2.50-1.70 (m, 2H), 1.67-1.62 (m, 2H), 1.39 (s, 9H); LC-MS purity: 88.4%; (M-Boc) measured value = 157.3; (Column: XSelect CSH C-18, 50×3.0mm, 3.5μm); Flow rate: 0.8 mL/min; mobile phase: 5 mM NH4OAc aqueous solution: acetonitrile (ACN).

References

[1] Patent: WO2015/48301, 2015, A1. Location in patent: Paragraph 00459
[2] Patent: US2009/105290, 2009, A1. Location in patent: Page/Page column 31
[3] Patent: WO2015/17305, 2015, A1. Location in patent: Page/Page column 64
[4] Patent: WO2016/65582, 2016, A1. Location in patent: Page/Page column 47
[5] Patent: WO2016/60941, 2016, A1. Location in patent: Page/Page column 52