Methyl iodide → 4-Methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1501800Notes

Reaction equation

[CH3:1][O:2][CH:3]1[C:7]2([CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH2:8]2)[C:6](=[O:20])[N:5]([C:21]2[CH2:22][O:23][C:24](=[O:27])[C:25]=2[CH3:26])[CH2:4]1.OC1C2(CCN(C(OC(C)(C)C)=O)CC2)C(=O)N(C2COC(=O)C=2C)C1.IC.[Al]>C(#N)C.[Ag]=O>[CH3:1][O:2][CH:3]1[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[C:6](=[O:20])[N:5]([C:21]2[CH2:22][O:23][C:24](=[O:27])[C:25]=2[CH3:26])[CH2:4]1

Participants

Conditions

Temperature: 58 °C

Procedure

tert-Butyl 4-methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (Enantiomer A and Enantiomer B): 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

Workup

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)

Sources & evidence

ORD record: ord-6dd607733de34e7b82d2dab3e8b7b2f7
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206198B2

Reaction notes

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