Sodium Carbonate → 3-Bromo-N-cyclopropyl-5-[(1E)-3-methoxyprop-1-en-1-yl]-4-methylbenzamide

HRID 337626Notes

Reaction equation

HRID 337626 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([Br:15])[C:13]=1[CH3:14])[C:5]([NH:7][CH:8]1[CH2:10][CH2:9]1)=[O:6].CC1(C)C(C)(C)OB(/[CH:24]=[CH:25]/[CH2:26][O:27][CH3:28])O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O>[Br:15][C:12]1[CH:11]=[C:4]([CH:3]=[C:2](/[CH:24]=[CH:25]/[CH2:26][O:27][CH3:28])[C:13]=1[CH3:14])[C:5]([NH:7][CH:8]1[CH2:10][CH2:9]1)=[O:6]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 162174432-[(1E)-3-methoxyprop-1-en-1-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 670619513,5-dibromo-N-cyclopropyl-4-methylbenzamide

Product 1

HCID 670620583-Bromo-N-cyclopropyl-5-[(1E)-3-methoxyprop-1-en-1-yl]-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3,5-dibromo-N-cyclopropyl-4-methylbenzamide (1 eq.) from the previous step and 4,4,5,5-tetramethyl-2-[(1E)-3-(methyloxy)-1-propen-1-yl]-1,3,2-dioxaborolane (1.1 eq.) in DMF (0.1 M) was added trans-bis(triphenylphosphine) palladium(II) bromide (0.05 eq.). The vessel was repeatedly evacuated and back-filled with nitrogen. Finally, 2 M aq. Na2CO3 (3 eq.) was added and the resulting mixture was heated at 100° C. for 1 h. The now black suspension was cooled to RT, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed further 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 yellow-orange oil.

Workup

  1. customThe vessel was repeatedly evacuated
  2. additionback-filled with nitrogen
  3. temperatureThe now black suspension was cooled to RT
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed further with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. customPurification of the crude product by way of flash chromatography (SiO2, 9:1 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record
ord-e879c1fcbcbf48a2a8ab96a4dcbe500c
Source dataset
uspto-grants-2014_11
Patent number
US08889714B2

Reaction notes

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