Methyl iodide → HCID 66618863, compound

HRID 406341Notes

Reaction equation

HRID 406341 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][O:12][C:11](=[O:15])[CH2:10]2)=[CH:5][CH:4]=1.F[C:19](F)(F)C1C=CC(B(O)O)=CC=1.O1CCC=CC1=O.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.IC>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH3:19][CH:10]1[CH:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:8][CH:7]=2)[CH2:14][CH2:13][O:12][C:11]1=[O:15]

Participants

10

Reactant 7

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 5206603393-45-1HCID 2724682Lithium diisopropylamideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 66779092HCID 66779092, compoundHCID 178418339Butyllithium

Product 1

HCID 66618863HCID 66618863, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Procedure

4-(4-Trifluoromethylphenyl)tetrahydropyran-2-one (995 mg) derived by the same method as in Preparation Example 2-10 from 4-(trifluoromethyl)phenylboronic acid (5.29 g) and 5,6-dihydro-2H-pyran-2-one was dissolved in tetrahydrofuran (10 mL). The solution was added dropwise at −78° C. to a lithium diisopropylamide solution previously prepared from n-butyllithium (3.91 mL) and diisopropylamine (1.46 mL) in tetrahydrofuran (30 mL). After stirring at the same temperature for 30 minutes, iodomethane (760 μL) and hexamethylphosphoramide (1.77 mL) were added and stirring was continued. After stirring for 30 minutes, the reaction solution was gradually heated to room temperature over three hours and 20 minutes. The reaction was terminated with saturated ammonium chloride aqueous solution. The organic layer was washed with brine and then dried over magnesium sulfate. Removal under reduced pressure gave an oil. The oil was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 50%) to obtain the title compound (500 mg).

Workup

  1. stirringstirring
  2. stirringAfter stirring for 30 minutes
  3. customThe reaction was terminated with saturated ammonium chloride aqueous solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customRemoval under reduced pressure
  7. customgave an oil
  8. customThe oil was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 50%)

Sources & evidence

ORD record
ord-8f6513a7ad9c4e368fca45892ab30d2d
Source dataset
uspto-grants-2014_06
Patent number
US08754100B2

Reaction notes

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