4-methyl-5-(oxiran-2-yl)isobenzofuran-1(3H)-one → HCID 49800469, compound

HRID 1187116Notes

Reaction equation

[CH:1]12[CH2:8][CH2:7][CH:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[CH2:9][CH:10]([C:12]1[CH:21]=[CH:20][C:15]2[C:16](=[O:19])[O:17][CH2:18][C:14]=2[C:13]=1[CH3:22])[OH:11].[CH3:23][C:24]1[C:32]2[CH2:31][O:30][C:29](=[O:33])[C:28]=2[CH:27]=[CH:26][C:25]=1[CH:34]1[CH2:36][O:35]1>CS(C)=O.O>[CH:1]12[CH2:8][CH2:7][CH:4]([N:5]([CH2:36][CH:34]([C:25]3[CH:26]=[CH:27][C:28]4[C:29](=[O:33])[O:30][CH2:31][C:32]=4[C:24]=3[CH3:23])[OH:35])[CH2:6]1)[CH2:3][N:2]2[CH2:9][CH:10]([C:12]1[CH:21]=[CH:20][C:15]2[C:16](=[O:19])[O:17][CH2:18][C:14]=2[C:13]=1[CH3:22])[OH:11]

Participants

Conditions

Temperature: 150 °C

Procedure

In four separate reactions, isomers A-D of 5-[2-(2,5-diazabicyclo[2.2.2]oct-2-yl)-1-hydroxyethyl]-4-methyl-2-benzofuran-1(3H)-one (about 100 mg, 0.33 mmol) and 4-methyl-5-oxiran-2-yl-2-benzofuran-1(3H)-one (95 mg, 0.50 mmol) in 2 mL DMSO was heated under microwave condition (150° C.) for 1 hr. After cooling to it, the mixtures were diluted with water (20 mL), extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine and dried over Na2SO4, then concentrated. The residues were purified by preparative TLC (MeOH/DCM=1:15) to obtain 5,5′-[2,5-diazabicyclo[2.2.2]octane-2,5-diylbis(1-hydroxyethane-2,1-diyl)]bis(4-methyl-2-benzofuran-1(3H)-one) as 4 mixtures of two isomers, which were separated by SFC chiral chromatography to obtain two single isomers for each (eight total).

Workup

temperatureAfter cooling to it
extractionextracted with EtOAc (3×20 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residues were purified by preparative TLC (MeOH/DCM=1:15)

Sources & evidence

ORD record: ord-3c6eebaa06ec488aabec2db221c5e88e
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673920B2

Reaction notes

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