Triethylamine → 5-[3-fluoro-4-(methylsulfanyl)phenyl]-1-(pyrazin-2-yl)-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione

HRID 1881923Notes

Reaction equation

HRID 1881923 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:10]([CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:11](=[O:14])[CH:12]=[CH2:13])[CH:5]=[CH:6][C:7]=1[S:8][CH3:9].[N:22]1[CH:27]=[CH:26][N:25]=[CH:24][C:23]=1[CH:28]=[O:29].C(N(CC)CC)C>C(O)C.[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:10]([CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:11](=[O:14])[CH2:12][CH2:13][C:28]([C:23]2[CH:24]=[N:25][CH:26]=[CH:27][N:22]=2)=[O:29])[CH:5]=[CH:6][C:7]=1[S:8][CH3:9]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 11274980Pyrazine-2-carbaldehydeHCID 593314814-[3-fluoro-4-(methylsulfanyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one

Product 1

HCID 593315445-[3-fluoro-4-(methylsulfanyl)phenyl]-1-(pyrazin-2-yl)-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dioneYield 75%

Reagents, catalysts & solvents 3

HCID 28333523-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chlorideCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[3-fluoro-4-(methylsulfanyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one (433 mg) in ethanol (7 mL) were added pyrazine-2-carbaldehyde (182 mg), 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride (41.5 mg) and triethylamine (84.1 μL), and the mixture was stirred with heating under reflux for 2 hr. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (438 mg, yield 75%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-hexane (2:1, volume ratio).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 2 hr
  3. washwashed with water
  4. dry with materialThe ethyl acetate layer was dried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d2e64f3d998d4ef1ab2b703939e02051
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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