Cyclopropylbenzene → (5-Chloro-6-methoxypyridin-2-yl)(4-cyclopropylphenyl)methanol

HRID 70516

Reaction equation

HRID 70516 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:15][CH2:14]2)=[CH:9][CH:8]=1.C1(C2C=CC=CC=2)CC1.[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([CH:34]=[O:35])=[N:30][C:31]=1[O:32][CH3:33]>O1CCCC1.O>[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([CH:34]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[OH:35])=[N:30][C:31]=1[O:32][CH3:33]

Participants

7

Reactant 4

HCID 70112CyclopropylbenzeneHCID 122213551-Bromo-4-cyclopropylbenzeneHCID 584528465-Chloro-6-methoxypicolinaldehydeHCID 178418339Butyllithium

Product 1

HCID 67399283(5-Chloro-6-methoxypyridin-2-yl)(4-cyclopropylphenyl)methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (1.65 M, 3 mL) was added dropwise to a solution of the mixture of 4-bromo-1-cyclopropylbenzene and cyclopropylbenzene (976 mg) 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 (732 mg) in tetrahydrofuran (9 mL) was added to the reaction solution at −78° C., and the mixture was stirred at the same temperature for three hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→1:10) to give (5-chloro-6-methoxypyridin-2-yl)(4-cyclopropylphenyl)methanol (765 mg).

Workup

  1. stirringthe mixture was stirred at the same temperature for three hours
  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. customThe solvent was then evaporated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→1:10)

Sources & evidence

ORD record
ord-1fec8c23d92843c58147f70a2606c192
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

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