Cesium carbonate → tert-butyl (6-(((2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl)oxy)-5-fluoropyridin-3-yl)carbamate

HRID 2277304Notes

Reaction equation

HRID 2277304 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:23])[C:5]([O:8][CH2:9][C@@H:10]([N:12]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])[CH3:11])=[N:6][CH:7]=1.[C:24](=[O:31])([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[NH2:25].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C1(C)C=CC=CC=1>[O:22]=[C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:20](=[O:21])[N:12]1[C@@H:10]([CH3:11])[CH2:9][O:8][C:5]1[N:6]=[CH:7][C:2]([NH:25][C:24](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:3][C:4]=1[F:23]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86731385HCID 86731385, compound

Product 1

HCID 86731386tert-butyl (6-(((2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl)oxy)-5-fluoropyridin-3-yl)carbamateYield 47.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-((2S)-1-((5-bromo-3-fluoropyridin-2-yl)oxy)propan-2-yl)-1H-isoindole-1,3(2H)-dione (3.10 g), tert-butyl carbamate (0.958 g), tris(dibenzylideneacetone)dipalladium(0) (0.374 g), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.710 g), cesium carbonate (5.33 g) and toluene (30 mL) was stirred at 110° C. overnight under an argon atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The combined organic layer were washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.62 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layer were washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-464fa5ce160b417899661593bdb2f18e
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

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