Ammonium Chloride → Cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methanone

HRID 2091325Notes

Reaction equation

HRID 2091325 reaction equation
[CH3:1][C:2]1[C:6]2=[N:7][CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=[C:5]2[S:4][C:3]=1[CH:15]=[O:16].[CH:17]1([Mg]Br)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.[Cl-].[NH4+].C[N+]1([O-])CCOCC1>O1CCCC1.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC.C(#N)C>[CH:17]1([C:15]([C:3]2[S:4][C:5]3[C:6](=[N:7][CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=3)[C:2]=2[CH3:1])=[O:16])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 82029Methyl morpholine oxideHCID 866627523-Methyl-6-(trifluoromethyl)thieno[3,2-b]pyridine-2-carbaldehydeHCID 178419651HCID 178419651, compound

Product 1

HCID 66778802Cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methanoneYield 42%

Reagents, catalysts & solvents 3

HCID 178419074HCID 178419074, compoundCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution (15 mL) of 3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridine-2-carbaldehyde (1.44 g) synthesized above in tetrahydrofuran was added 1.0M solution (8.81 mL) of cyclohexylmagnesium bromide in tetrahydrofuran at 0° C., and the mixture was stirred for 1 hr under argon atmosphere. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (10-50% ethyl acetate/hexane) to give a yellow oil. To a mixture of the obtained oil, 4-methylmorpholine N-oxide (817 mg) and acetonitrile (20 mL) was added tetrapropylammonium perruthenate (108 mg), and the mixture was stirred at room temperature for 1 hr, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-10% ethyl acetate/hexane) to give the title object compound (805 mg, 42%) as a yellow solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (10-50% ethyl acetate/hexane)
  8. customto give a yellow oil
  9. stirringthe mixture was stirred at room temperature for 1 hr
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (0-10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ffb8e745fc984c09b8998f4013f3af61
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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