HCID 59790325, compound → HCID 59790327, compound

HRID 2240954Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:29])[CH2:4][CH:5]1[CH2:8][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15](=[O:28])[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[CH:20][CH:19]=3)=[O:17])[CH:10]=2)[CH2:6]1>CS(C)=O.CC#N.CC#N.Cl[Pd]Cl>[CH3:1][O:2][C:3](=[O:29])[CH:4]=[C:5]1[CH2:8][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15](=[O:28])[C:16]([C:18]3[CH:19]=[CH:20][C:21]([O:24][CH:25]([F:26])[F:27])=[CH:22][CH:23]=3)=[O:17])[CH:10]=2)[CH2:6]1

Participants

Conditions

Temperature: 145 °C

Procedure

In a 250 ml round bottom flask was dissolved (3-{3-[2-(4-Difluoromethoxy-phenyl)-2-oxo-acetyl]-phenyl}-cyclobutyl)-acetic acid methyl ester (1.348 g, 3.66 mmol) in DMSO (45 mL). Bis(acetonitrile)dichloropalladium was added and the flask heated (oil bath; 145° C.) for 4 hours. More Bis(acetonitrile)dichloro-palladium (90 mg) was added and heating was continued for another 4 hours. The crude material was partitioned between water (50 mls) and dichloromethane. Dichloromethane extracts (2×50 mls) were combined and concentrated onto silica gel. Purification by column chromatography (gradient; 10-20% EtOAc in hexanes) afforded 1.17 gm of a yellow oil (80%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.90-3.02 (m, 1H) 3.05-3.16 (m, 1H) 3.22-3.28 (m, 1H) 3.49-3.59 (m, 1H) 3.62-3.64 (m, 3H) 3.72-3.82 (m, 1H) 5.73-5.77 (m, 1H) 7.39 (dt, J=9.3, 2.5 Hz, 2H) 7.46 (t, J=73.0 Hz, 2H) 7.59 (t, J=7.8 Hz, 1H) 7.72-7.80 (m, 2H) 7.85 (t, J=1.9 Hz, 1H) 8.02 (dt, J=9.4, 2.6 Hz, 2H); MS (ES) m/z 401.1 [M+H]+

Workup

temperatureheating
customThe crude material was partitioned between water (50 mls) and dichloromethane
concentrationconcentrated onto silica gel
customPurification by column chromatography (gradient; 10-20% EtOAc in hexanes)

Sources & evidence

ORD record: ord-5b8d4af32ab4447597bff756cd26043c
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723368B2

Reaction notes

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