Dimethylformamide → N-Cyclopropyl-5-[(1E)-3-methoxy-1-propen-1-yl]-2,3-dimethylbenzamide

HRID 337616Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH3:15])[C:5]([CH3:14])=[C:6]([CH:13]=1)[C:7]([NH:9][CH:10]1[CH2:12][CH2:11]1)=[O:8].CC1(C)C(C)(C)OB(/[CH:24]=[CH:25]/[CH2:26][O:27][CH3:28])O1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>O.C(O)CC>[CH:10]1([NH:9][C:7](=[O:8])[C:6]2[CH:13]=[C:2](/[CH:24]=[CH:25]/[CH2:26][O:27][CH3:28])[CH:3]=[C:4]([CH3:15])[C:5]=2[CH3:14])[CH2:12][CH2:11]1

Participants

Conditions

Temperature: 100 °C

Procedure

5-Bromo-N-cyclopropyl-2,3-dimethylbenzamide (1 eq.) from the previous step and 4,4,5,5-tetramethyl-2-[(1E)-3-(methyloxy)-1-propen-1-yl]-1,3,2-dioxaborolane (1.5 eq.) were combined in a 5:1 (v/v) mixture of DMF:n-PrOH (0.1 M). To this solution was then added trans-bis(triphenylphosphine) palladium(II) bromide (0.05 eq.) and the vessel was repeatedly evacuated and back-filled with nitrogen. Finally, 2 M aq. Na2CO3 (3 eq.) was added and the resulting biphasic suspension was heated at 100° C. for 18 h. The now black suspension was cooled to RT, diluted with water and extracted with ether. The combined organic extracts were then washed with water and brine, dried over Na2SO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product by way of flash chromatography (SiO2, 9:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a white solid.

Workup

additionback-filled with nitrogen
temperatureThe now black suspension was cooled to RT
extractionextracted with ether
washThe combined organic extracts were then washed with water and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate concentrated in vacuo
customPurification of the crude product by way of flash chromatography (SiO2, 9:1 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record: ord-da11b5e4b52146ba9783496e6c2a34df
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889714B2

Reaction notes

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