Dimethylformamide → HCID 57736424, compound

HRID 1641707Notes

Reaction equation

HRID 1641707 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH:9]([C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=2[F:27])[S:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=2)=[CH:4][N:3]=1.CCCCCC.C([Li])CCC.CN(C)[CH:41]=[O:42]>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[F:27][C:21]1[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:20]=1[CH:9]([S:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=1)[C:5]1[C:6]([CH3:8])=[CH:7][C:2]([CH:41]=[O:42])=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8058HexaneHCID 57736423HCID 57736423, compoundHCID 178418339Butyllithium

Product 1

HCID 57736424HCID 57736424, compoundYield 75.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 2-bromo-5-[(2,5-difluorophenyl)[(4-ethoxyphenyl)thio]methyl]-4-methylpyridine (1.18 g, 2.62 mmol) in toluene (30 ml), a hexane solution of n-butyllithium (1.54 M, 2.04 ml, 3.14 mmol) was added in an argon atmosphere at −78° C. The reaction mixture was stirred for 30 minutes at −40° C., and then cooled again to −78° C., and N,N-dimethylformamide (0.243 ml, 3.14 mmol) was added thereto. After completion of dropwise addition, the reaction mixture was allowed to warm to −40° C., and water was added at the same temperature. Ethyl acetate was added to the reaction mixture, the organic layer was separated, and then the organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the obtained residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=10:1 was concentrated under reduced pressure to obtain the title compound (786 mg, 1.97 mmol, 75%) as a white solid.

Workup

  1. temperaturecooled again to −78° C.
  2. additionAfter completion of dropwise addition
  3. temperatureto warm to −40° C.
  4. customthe organic layer was separated
  5. washthe organic layer was washed with saturated brine
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe fraction obtained from an elution with hexane
  10. concentrationethyl acetate=10:1 was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1e28cf48a63141caa8421a5434870674
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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