Methyl iodide → tert-Butyl 4-methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

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Reaktionsgleichung

[OH:1][CH:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[C:5](=[O:19])[N:4]([C:20]2[CH2:21][O:22][C:23](=[O:26])[C:24]=2[CH3:25])[CH2:3]1.I[CH3:28].[Al]>C(#N)C.[Ag]=O>[CH3:28][O:1][CH:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:8][CH2:7]2)[C:5](=[O:19])[N:4]([C:20]2[CH2:21][O:22][C:23](=[O:26])[C:24]=2[CH3:25])[CH2:3]1

Komponenten

Reaktionsbedingungen

Temperatur: 58 °C

Versuchsvorschrift

To a solution of tert-butyl 4-hydroxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (100 mg, 0.273 mmol) in acetonitrile (1 mL) was added iodomethane (171 μL, 2.73 mmol) and silver oxide (69.6 mg, 0.300 mmol). The vial was sealed, wrapped with aluminum foil, and stirred at 58° C. for 15 h. The reaction mixture was filtered through CELITE®, concentrated to give the crude product, which was purified by column chromatography (0-10% MeOH/DCM) to afford the title compound as a mixture of enantiomers. LC/MS: [(M+1)]+=381. The racemic mixture was separated by SFC-HPLC, using the following conditions: chiralcel AD-H, 2×25 cm, 15% MeOH, 60 mL/min to afford faster eluting Enantiomer A: LC/MS: [(M+1)]+=381; and slower eluting Enantiomer B: LC/MS: [(M+1)]+=381

Aufarbeitung

customThe vial was sealed
filtrationThe reaction mixture was filtered through CELITE®
concentrationconcentrated
customto give the crude product, which
customwas purified by column chromatography (0-10% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag: ord-fe269afc23e74e9db5497b3c7a210532
Quelldatensatz: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08952166B2

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