Methyl vinyl ketone → Tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate

HRID 2403647Notes

Reaction equation

[CH:1]([C:3]([CH3:5])=[O:4])=[CH2:2].[CH:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)=O.[OH-].[K+].C1CCCCC1>O1CCCC1.C(O)C>[O:4]=[C:3]1[CH2:5][CH2:6][C:8]2([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:2]=[CH:1]1

Participants

Conditions

Temperature: -5 °C

Procedure

Methyl vinyl ketone (146 mL, 1.78 mol) was added to a solution of tert-butyl 4-formylpiperidine-1-carboxylate (375 g, 1.76 mol) in tetrahydrofuran (18 L). The reaction mixture was cooled to −5° C. and a solution of potassium hydroxide in ethanol (3N, 0.243 L) was added dropwise over 10 minutes. The reaction mixture was allowed to warm to room temperature and stirred for 16 hours. Cyclohexane (10 L) was added and the solution was washed with saturated sodium chloride (3×10 L). The organic layer was concentrated to an oil. This oil was dissolved in 2 L of 80:20 cyclohexane/ethyl acetate and filtered through Celite® to remove the insoluble material. The filtrate was purified via flash column chromatography (30% ethyl acetate/hexanes) to afford the product as an oil. The oil was triturated in hexanes to afford the title compound as a colorless solid (131 g, 28%).

Workup

temperatureto warm to room temperature
washthe solution was washed with saturated sodium chloride (3×10 L)
concentrationThe organic layer was concentrated to an oil
dissolutionThis oil was dissolved in 2 L of 80:20 cyclohexane/ethyl acetate
filtrationfiltered through Celite®
customto remove the insoluble material
customThe filtrate was purified via flash column chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-6f63cbeef39b4411834cbc675dd48d2c
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802688B2

Reaction notes

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