Ammonium Chloride → (6-Bromo-4-methylpyridin-3-yl)(2,5-difluorophenyl)methanol

HRID 1641673

Reaction equation

HRID 1641673 reaction equation
C([Li])CCC.[Br:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10](Br)=[CH:9][N:8]=1.[F:15][C:16]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:17]=1[CH:18]=[O:19].[Cl-].[NH4+]>C(OCC)C.CCCCCC>[Br:6][C:7]1[N:8]=[CH:9][C:10]([CH:18]([C:17]2[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:16]=2[F:15])[OH:19])=[C:11]([CH3:13])[CH:12]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 1376632,5-DifluorobenzaldehydeHCID 27344292,5-Dibromo-4-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 57736414(6-Bromo-4-methylpyridin-3-yl)(2,5-difluorophenyl)methanolYield 34%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

In an argon atmosphere, a hexane solution of n-butyllithium M, 8.22 ml, 13.2 mmol) was added to a solution of 2,5-dibromo-4-methylpyridine (3.00 g, 12.0 mmol) in diethyl ether (120 ml) at −78° C. After stirring the reaction mixture for 30 minutes, 2,5-difluorobenzaldehyde (1.34 ml, 12.0 mmol) was added. After stirring for 1 hour at the same temperature, saturated aqueous ammonium chloride was added at room temperature. After the organic layer was separated, the organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=4:1 was concentrated under reduced pressure, to obtain the title compound (1.26 g, 4.01 mmol, 34%) as a white solid.

Workup

  1. additionwas added at room temperature
  2. customAfter the organic layer was separated
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe fraction obtained from an elution with hexane
  7. concentrationethyl acetate=4:1 was concentrated under reduced pressure

Sources & evidence

ORD record
ord-34104e0a00724cbab9759f5380b05975
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Linked notes

Loading…