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

HRID 1848448Notes

Reaction equation

[CH3:1][CH:2]1[CH2:6][C:5]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:4](=[O:19])[NH:3]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].O.Br[C:70]1[CH2:71][C:72](=[O:75])[O:73][CH:74]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][CH:2]1[CH2:6][C:5]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:4](=[O:19])[N:3]1[C:70]1[CH2:74][O:73][C:72](=[O:75])[CH:71]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of tert-butyl 3-methyl-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (I-13) (505 mg, 1.88 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (109 mg, 0.188 mmol), palladium(II) acetate (21 mg, 0.094 mmol), potassium carbonate (520 mg, 3.76 mmol), water (102 μl, 5.65 mmol) and commercially available 4-bromofuran-2-one (368 mg, 2.26 mmol) in toluene (13 mL) was degassed and then heated at 60° C. for 16 hours. The mixture was filtered through a pad of CELITE®, and the filter cake was washed with ethyl acetate. The filtrates were concentrated and the residue was purified by column chromatography eluting with 10-100% ethyl acetate/hexane gradient to give the title compound. LC-MS (IE, m/z): 373.3 (M+23)+.

Workup

customwas degassed
filtrationThe mixture was filtered through a pad of CELITE®
washthe filter cake was washed with ethyl acetate
concentrationThe filtrates were concentrated
customthe residue was purified by column chromatography
washeluting with 10-100% ethyl acetate/hexane gradient

Sources & evidence

ORD record: ord-8d1e7d7c692c4289b1f095dbc233122d
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952166B2

Reaction notes

Loading…