4-methyl-5-(oxiran-2-yl)isobenzofuran-1(3H)-one → HCID 49800470, compound

HRID 1187115Notes

Reaction equation

[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([CH2:9][CH:10]([C:12]1[CH:21]=[CH:20][C:15]3[C:16](=[O:19])[O:17][CH2:18][C:14]=3[C:13]=1[CH3:22])[OH:11])[CH2:2]2.[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[N:8]([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])[CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([CH2:9][CH:10]([C:12]1[CH:21]=[CH:20][C:15]3[C:16](=[O:19])[O:17][CH2:18][C:14]=3[C:13]=1[CH3:22])[OH:11])[CH2:2]2

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of isomer (37B) of 5-[2-(3,8-diazabicyclo[3.2.1]oct-3-yl)-1-hydroxyethyl]-4-methyl-2-benzofuran-1(3H)-one (45 mg, 0.149 mmol) and 4-methyl-5-oxiran-2-yl-2-benzofuran-1(3H)-one (57 mg, 0.210 mmol) in 2 mL DMSO was heated under microwave condition (150° C.) for 1 hr. After cooling to rt., the mixture was diluted with water (50 mL), and extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine and dried over Na2SO4, then concentrated. The residue was purified by prep-TLC (MeOH/DCM=1:15) and then separated by SFC chiral chromatography to obtain two separated isomers C and D of 5,5′-[3,8-diazabicyclo[3.2.1]octane-3,8-diylbis(1-hydroxyethane-2,1-diyl)]bis(4-methyl-2-benzofuran-1(3H)-one).

Workup

temperatureAfter cooling to rt
extractionextracted with EtOAc (3×50 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue was purified by prep-TLC (MeOH/DCM=1:15)
customseparated by SFC chiral chromatography

Sources & evidence

ORD record: ord-ca423d6e43e4484ba66861d5e1cd4eeb
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673920B2

Reaction notes

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