Dimethylformamide → 6-Fluoro-2,3-dihydro-3,3-dimethyl-1H-isoindol-1-one

HRID 2277627Notes

Reaction equation

HRID 2277627 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([NH2:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C.CN([CH:25]=[O:26])C>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:8][C:6]1[CH:7]=[C:2]2[C:3]([C:9]([CH3:11])([CH3:10])[NH:12][C:25]2=[O:26])=[CH:4][CH:5]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 83712564HCID 83712564, compound

Product 1

HCID 717440006-Fluoro-2,3-dihydro-3,3-dimethyl-1H-isoindol-1-oneYield 8.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 1-(2-bromo-4-fluoro-phenyl)-1-methyl-ethylamine (1.5 g, 6.52 mmol), Pd(dppf)Cl2 (0.15 g), DIPEA (2.52 g, 19.6 mmol) in DMF (20 mL) was stirred in an autoclave under 2 MPa of CO (g) at 130° C. for 16 hours. After it was cooled to room temperature, the reaction mixture was diluted with EtOAc (300 mL). The organic layer was washed with brine, filtered, and concentrated under reduced pressure to give a crude product which was purified by chromatography to give the title compound (100 mg, yield 8.6%) as a brown solid.

Workup

  1. temperatureAfter it was cooled to room temperature
  2. washThe organic layer was washed with brine
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give a crude product which
  6. customwas purified by chromatography

Sources & evidence

ORD record
ord-0b967671d7114d9e8a398b900a9cc43a
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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