Hydrochloric Acid → 7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine

HRID 2202223Notes

Reaction equation

HRID 2202223 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:13](=[C:14]([F:16])[CH:15]=1)[C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10]2)(=O)=O.C1(C(C2C=CC=CC=2)=[NH:28])C=CC=CC=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].Cl.[OH-].[Na+]>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>[F:16][C:14]1[CH:15]=[C:7]([NH2:28])[CH:8]=[C:9]2[C:13]=1[C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10]2

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 1186227557-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl trifluoromethanesulfonate

Product 1

HCID 1186227997-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amineYield 65%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl trifluoromethanesulfonate (5.18 g, 16.59 mmol), diphenylmethanimine (3.61 g, 19.91 mmol), Pd2(dba)3 (0.759 g, 0.83 mmol), BINAP (1.033 g, 1.66 mmol), sodium tert-butoxide (2.391 g, 24.88 mmol) and toluene (75 mL) was stirred at 80° C. for 2 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in THF (200 mL), LN hydrochloric acid (83 mL, 82.94 mmol) was added thereto, and the mixture was stirred at room temperature for 30 min, and basified with 1N aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane) to give 7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine (1.92 g, 10.71 mmol, 65%) as an orange oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe obtained residue was dissolved in THF (200 mL)
  5. stirringthe mixture was stirred at room temperature for 30 min
  6. extractionThe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4a28604fdbcb48a3bc48045bed3ba71f
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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