HCID 86619855, compound → HCID 16119582, compound

HRID 1694412Notes

Reaction equation

HRID 1694412 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:14]2[CH2:17][CH:16]([C:18]([NH:20][CH2:21][CH:22]([CH3:24])[CH3:23])=[O:19])[CH:15]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1.[H][H]>CCO.[Pd].CCOC(C)=O>[CH2:21]([NH:20][C:18]([CH:16]1[CH2:17][CH:14]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][N:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)=[C:2]([F:1])[CH:3]=2)[CH2:15]1)=[O:19])[CH:22]([CH3:24])[CH3:23]

Participants

6

Reactant 2

HCID 86619855HCID 86619855, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 16119582HCID 16119582, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Crude intermediate 16, 3-(3-fluoro-4-((pyrrolidin-1-yl)methyl)phenyl)-N-isobutylcyclobut-2-enecarboxamide prepared above was dissolved in EtOH (100 mL) and added to a hydrogenation bottle containing 10% palladium on carbon slurried in EtOH (˜5 mL). The mixture was shaken at room temperature under 45 psi of hydrogen for 2 h, filtered through diatomaceous earth with an EtOH rinse and concentrated to yield an orange oil. This was dissolved in EtOAc (150 mL) and washed with aqueous K2CO3 and brine, dried over MgSO4 and concentrated to afford 3.29 g of waxy orange solid. Flash chromatography on a 2.5″×4″ silica gel column eluting with 1000 mL EtOAc and 500 mL 10% MeOH/EtOAc afforded 1.90 g (54%) of the title compound as a yellow tinged solid: Rf=0.26 (20% MeOH/EtOAc).

Workup

  1. additionadded to a hydrogenation bottle
  2. filtrationfiltered through diatomaceous earth with an EtOH
  3. washrinse
  4. concentrationconcentrated
  5. customto yield an orange oil
  6. washwashed with aqueous K2CO3 and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto afford 3.29 g of waxy orange solid
  10. washFlash chromatography on a 2.5″×4″ silica gel column eluting with 1000 mL EtOAc and 500 mL 10% MeOH/EtOAc

Sources & evidence

ORD record
ord-b5d72b90c63040bf90d1d8ef764e8df2
Source dataset
uspto-grants-2012_04
Patent number
US08158673B2

Reaction notes

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