Ammonium Chloride → 3-cyclopropyl-2-methoxy-6-[(E)-1-[4-(methylsulfanyl)phenyl]-2-(tetrahydrofuran-3-yl)ethenyl]pyridine

HRID 70598Notes

Reaction equation

HRID 70598 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].C1(N2C(S([CH2:25][CH:26]3[CH2:30][CH2:29][O:28][CH2:27]3)(=O)=O)=NN=N2)C=CC=CC=1.[CH:31]1([C:34]2[CH:35]=[CH:36][C:37]([C:42]([C:44]3[CH:49]=[CH:48][C:47]([S:50][CH3:51])=[CH:46][CH:45]=3)=O)=[N:38][C:39]=2[O:40][CH3:41])[CH2:33][CH2:32]1.[Cl-].[NH4+]>O1CCCC1>[CH:31]1([C:34]2[C:39]([O:40][CH3:41])=[N:38][C:37](/[C:42](/[C:44]3[CH:49]=[CH:48][C:47]([S:50][CH3:51])=[CH:46][CH:45]=3)=[CH:25]/[CH:26]3[CH2:30][CH2:29][O:28][CH2:27]3)=[CH:36][CH:35]=2)[CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 58452640HCID 58452640, compoundHCID 58452884HCID 58452884, compound

Product 1

HCID 674005353-cyclopropyl-2-methoxy-6-[(E)-1-[4-(methylsulfanyl)phenyl]-2-(tetrahydrofuran-3-yl)ethenyl]pyridineYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (5.14 mL) was added to a solution of 1-phenyl-5-[(tetrahydrofuran-3-ylmethyl)sulfonyl]-1H-tetrazole obtained in Reference Example 3-6 (1.51 g) in tetrahydrofuran (15 mL) in a nitrogen gas stream at −78° C., and the mixture was stirred at −78° C. for one hour. A solution of (5-cyclopropyl-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanone obtained in Reference Example 1-51 (700 mg) in tetrahydrofuran (10 mL) was added, and the mixture was stirred at −78° C. to 0° C. 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 saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→7:3) to give 3-cyclopropyl-2-methoxy-6-[(E)-1-[4-(methylsulfanyl)phenyl]-2-(tetrahydrofuran-3-yl)ethenyl]pyridine (122 mg, 14%) as a colorless oil.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at −78° C. to 0° C. for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→7:3)

Sources & evidence

ORD record
ord-9ab7061f8e5146ca83caca16e08f9726
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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