Methanol → HCID 21904789, compound

HRID 1394093Notes

Reaction equation

HRID 1394093 reaction equation
[CH:1]([N-:4][CH:5]([CH3:7])C)([CH3:3])C.[Li+].[F:9][C:10]([F:25])([F:24])[C:11]1[C:12](N2CCC(=O)CC2)=[N:13][CH:14]=[CH:15][CH:16]=1.[C:26]1(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)[CH:31]=CC=CC=1.C(N(CC)CC)C.[CH3:54][OH:55].[C]=[O:57]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[F:25][C:10]([F:9])([F:24])[C:11]1[C:12]([N:4]2[CH2:1][CH:3]=[C:31]([C:26]([O:55][CH3:54])=[O:57])[CH2:7][CH2:5]2)=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

10

Reactant 6

HCID 887MethanolHCID 8471TriethylamineHCID 142176Phenyl triflimideHCID 2724682Lithium diisopropylamideHCID 219047511-(3-(Trifluoromethyl)pyridin-2-YL)piperidin-4-oneHCID 178418416HCID 178418416, compound

Product 1

HCID 21904789HCID 21904789, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

Lithium diisopropyl amide (37.3 mmol) in THF (75 mL) at −78° C. was treated with 1-[3-(trifluoromethyl)pyridin-2-yl]piperidin-4-one (8.30 g, 34.0 mmol) in THF (25 mL) and stirred for 45 minutes. The mixture was treated with solid PhNTf2 (14.0 g, 39.1 mmol), stirred for 1 hour, and concentrated under reduced pressure. The residue was diluted with ethyl acetate:hexanes (1:1), washed with 1N NaOH, dried (Na2SO4), filtered through a silica plug, and the filtrate was concentrated under reduced pressure. The residue, triethylamine (14.2 mL, 102 mmol), and PdCl2(PPh3)2 (0.944 g, 1.34 mmol) were combined in methanol (7.00 mL, 173 mmol) and DMF (100 mL) and saturated with carbon monoxide gas (bubbling 15 minutes). The mixture was heated at 80° C. under a carbon monoxide atmosphere (1 atm) overnight. The mixture was concentrated to half volume, diluted with diethyl ether, washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (6% ethyl acetate/hexanes) to provide the title compound.

Workup

  1. stirringstirred for 1 hour
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with ethyl acetate:hexanes (1:1)
  4. washwashed with 1N NaOH
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered through a silica plug
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. concentrationThe mixture was concentrated to half volume
  9. additiondiluted with diethyl ether
  10. washwashed with water, brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe residue was purified by flash chromatography (6% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2f650fc2ea484a069f7024a4d4ac072b
Source dataset
uspto-grants-2008_03
Patent number
US07348343B2

Reaction notes

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