Ammonium Chloride → (5-Chloro-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanol

HRID 70497

Reaction equation

HRID 70497 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=1.[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([CH:24]=[O:25])=[N:20][C:21]=1[O:22][CH3:23].[Cl-].[NH4+]>O1CCCC1>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([CH:24]([C:7]2[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=2)[OH:25])=[N:20][C:21]=1[O:22][CH3:23]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 660374-BromothioanisoleHCID 584528465-Chloro-6-methoxypicolinaldehydeHCID 178418339Butyllithium

Product 1

HCID 67396108(5-Chloro-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanolYield 72.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (2.64 M, 2.9 mL) was added to a solution of 4-bromothioanisole (1.61 g) in tetrahydrofuran (20 mL) at −78° C. in a nitrogen atmosphere, and the mixture was stirred at the same temperature for 30 minutes. A solution of 5-chloro-6-methoxypyridine-2-carbaldehyde (1.14 g) in tetrahydrofuran (10 mL) was added to the reaction solution, followed by stirring for one hour. The reaction solution was poured into a saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered, after which the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→4:1) to give (5-chloro-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanol as a pale yellow oil (1.42 g).

Workup

  1. stirringby stirring for one hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationafter which the filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→4:1)

Sources & evidence

ORD record
ord-f806ee9f51c84a7e8397092246675d0c
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

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