Diisopropylethylamine → Tert-butyl 2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate

HRID 1253710Notes

Reaction equation

[CH2:1]1[C:5]2([CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][NH:2]1.C(N(C(C)C)C(C)C)C.Cl.Cl[C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1.C([O-])(O)=O.[Na+]>CC(O)C.C(OCC)(=O)C>[N:32]1[CH:33]=[CH:34][C:29]([N:2]2[CH2:3][CH2:4][C:5]3([CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]3)[CH2:1]2)=[CH:30][CH:31]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-8-carboxylate (10.402 mmol, 1.0 eq.), N-ethyl-diisopropylamine (4.0 eq.) and 4-chloropyridine hydrochloride (3.0 eq.) in 2-propanol (20 ml) was stirred at 90° C. overnight. Ethyl acetate and sat. NaHCO3 solution were added and the aqueous phase was extracted with ethyl acetate a further 4×. The combined organic phases were washed 1× with sat. NaCl solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 500:100:2). Yield: 45%

Workup

extractionthe aqueous phase was extracted with ethyl acetate a further 4×
washThe combined organic phases were washed 1× with sat. NaCl solution
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 500:100:2)

Sources & evidence

ORD record: ord-f45efdf50f5f48d8b7e9e5b3de494b9d
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455475B2

Reaction notes

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