Dimethylformamide → HCID 86076475, compound

HRID 606880Notes

Reaction equation

HRID 606880 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[C:11]([C:13]#[C:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([F:22])[CH:16]=2)[CH:12]=1.CN(C)[CH:25]=[O:26].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:22][C:17]1[CH:16]=[C:15]([C:14]#[C:13][C:11]2[CH:12]=[C:7]([CH:25]=[O:26])[CH:8]=[N:9][CH:10]=2)[CH:20]=[CH:19][C:18]=1[F:21]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 67047746HCID 67047746, compoundHCID 178418339Butyllithium

Product 1

HCID 86076475HCID 86076475, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Add a 2.5 M solution of butyllithium in hexanes (3.18 mL, 7.96 mmol) to anhydrous toluene (11 mL) at −78° C. Allow the internal temperature to return to −78° C., then add 3-bromo-5-(3,4-difluorophenylethynyl)-pyridine (1.56 g, 5.30 mmol), (prepared essentially as described in EXAMPLE 100), dissolved in anhydrous toluene (11 mL) at such a rate to maintain the reaction temperature below −60° C. Stir for 5 min, add N,N-dimethylformamide (0.47 g, 6.37 mmol) dropwise at a rate so as to maintain the reaction temperature below 60° C. Stir for 20 min, warm to 0° C. and add an aqueous saturated solution of ammonium chloride and ethyl acetate. Stir for 5 min and separate the layers. Dry (magnesium sulfate), filter and concentrate. Purify the residue by silica gel chromatography, eluting with 30:70 ethyl acetate:hexanes to give the title compound as a white solid (0.780 g, 61%).

Workup

  1. customto return to −78° C.
  2. temperatureto maintain the reaction temperature below −60° C
  3. temperatureto maintain the reaction temperature below 60° C
  4. stirringStir for 20 min
  5. stirringStir for 5 min
  6. customseparate the layers
  7. dry with materialDry (magnesium sulfate)
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify the residue by silica gel chromatography
  11. washeluting with 30:70 ethyl acetate

Sources & evidence

ORD record
ord-5116ee1bfe8c4509b1723d9dc08888ac
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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