Diethyl Ether → HCID 86716068, compound

HRID 627481Notes

Reaction equation

HRID 627481 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C[Mg]Br.CCOCC.[F:16][C:17]1[CH:18]=[C:19]([CH:26]=[CH:27][N:28]=1)[C:20](N(OC)C)=[O:21]>C(Cl)Cl>[F:16][C:17]1[CH:18]=[C:19]([C:20]([C:2]2[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=2)=[O:21])[CH:26]=[CH:27][N:28]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 44818651HCID 44818651, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 86716068HCID 86716068, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
4 °C

Procedure

To a solution of 5-bromo-1-methyl-1H-imidazole (0.964 g, 5.99 mmol) in CH2Cl2 (6 mL) at room temperature was added 3.0 Methylmagnesium bromide in Et2O (2.0 mL, 6.00 mmol) dropwise. The mixture changed to a white suspension briefly then to clear yellow. After 15 min stirring, the mixture was cooled to 4° C. A solution of 2-fluoro-N-methoxy-N-methylisonicotinamide (1.05 g, 5.70 mmol, Intermediate 13, step a) in CH2Cl2 (6 mL) was introduced via cannula and some hard solid formed. The cooling bath was removed, and the mixture was stirred for 2 days. NH4Cl (aqueous) was added, the organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was diluted with small amount of CH2Cl2. The undissolved solid was filtered, washed with Et2O, and dried under vacuum to provide the title compound as a white solid. The filtrate was concentrated and purified by flash column chromatography (40 g silica gel column, 100% EtOAc) to give more title compound.

Workup

  1. customsome hard solid formed
  2. customThe cooling bath was removed
  3. stirringthe mixture was stirred for 2 days
  4. additionNH4Cl (aqueous) was added
  5. customthe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe residue was diluted with small amount of CH2Cl2
  11. filtrationThe undissolved solid was filtered
  12. washwashed with Et2O
  13. customdried under vacuum

Sources & evidence

ORD record
ord-a05b7f510e6f4716a0b01c3b28c0d4da
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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