Cesium carbonate → 1H-Isoindol-1-one, 6-fluoro-2,3-dihydro-2-[5-(hydroxymethyl)-3-pyridinyl]-3,3-dimethyl-

HRID 2277628Notes

Reaction equation

HRID 2277628 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:13])([CH3:12])[NH:7][C:8]2=[O:11])=[CH:4][CH:3]=1.Br[C:15]1[CH:16]=[C:17]([CH2:21][OH:22])[CH:18]=[N:19][CH:20]=1.[C@H]1(N)CCCC[C@@H]1N.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:13])([CH3:12])[N:7]([C:15]3[CH:20]=[N:19][CH:18]=[C:17]([CH2:21][OH:22])[CH:16]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 4793071,2-Diaminocyclohexane, (+)-HCID 2784733(5-Bromo-3-pyridinyl)methanolHCID 717440006-Fluoro-2,3-dihydro-3,3-dimethyl-1H-isoindol-1-one

Product 1

HCID 866859461H-Isoindol-1-one, 6-fluoro-2,3-dihydro-2-[5-(hydroxymethyl)-3-pyridinyl]-3,3-dimethyl-Yield 92%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-fluoro-3,3-dimethyl-2,3-dihydro-isoindol-1-one (intermediate A-20 [B], 35.8 mg, 0.2 mmol), (5-bromo-pyridin-3-yl)-methanol (74.8 mg, 0.4 mmol), CuI (3.8 mg, 0.02 mmol), (1S,2S)-cyclohexane-1,2-diamine (4.5 mg, 0.04 mmol) and Cs2CO3 (130 mg, 0.4 mmol) were dissolved in dioxane (5 mL). The reaction mixture was subjected to microwave reaction at 140° C. for 1 hour before it was poured into H2O (50 mL) and extracted with EtOAc (2×25 mL). The organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product (52 mg, 92%) as a solid. MS: 287.1 (M+H+).

Workup

  1. customreaction at 140° C. for 1 hour before it
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe organic layer was washed with brine
  4. customdried over anhy
  5. filtrationNa2SO4, filtered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e59165b7fa284a9a9b415e6c82ec5bea
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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