Benzophenone imine → 5-(Cyclopropylmethoxy)pyridin-2-amine

HRID 1026312Notes

Reaction equation

HRID 1026312 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[CH:4][N:3]=1.C1(C(C2C=CC=CC=2)=[NH:20])C=CC=CC=1.CC(C)([O-])C.[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].C1(C)C=CC=CC=1>[CH:10]1([CH2:9][O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:20])=[N:3][CH:4]=2)[CH2:12][CH2:11]1

Participants

6

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 578217962-Bromo-5-(cyclopropylmethoxy)pyridine

Product 1

HCID 284136605-(Cyclopropylmethoxy)pyridin-2-amineYield 90.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-5-(cyclopropylmethoxy)pyridine (5.65 g), tris(dibenzylideneacetone)dipalladium(0) (454 mg), 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (925 mg), 1,1-diphenylmethanimine (5.42 g), sodium t-butoxide (3.33 g) and toluene (50 mL) was stirred at 80° C. for 3 hr under an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with THF (15 mL). 1M Hydrochloric acid (15 mL) was added thereto, and the mixture was stirred at room temperature for 30 min. 6M Hydrochloric acid (6 mL) was added thereto, and the organic layer was separated from the aqueous layer. The separated organic layer was extracted with 1M hydrochloric acid. The combined aqueous layer was neutralized with 8M aqueous sodium hydroxide solution, and extracted twice with ethyl acetate. The combined organic layer was 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), and recrystallized (hexane/diethyl ether) to give the title compound as colorless crystals (3.67 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with THF (15 mL)
  3. addition1M Hydrochloric acid (15 mL) was added
  4. stirringthe mixture was stirred at room temperature for 30 min
  5. addition6M Hydrochloric acid (6 mL) was added
  6. customthe organic layer was separated from the aqueous layer
  7. extractionThe separated organic layer was extracted with 1M hydrochloric acid
  8. extractionextracted twice with ethyl acetate
  9. washThe combined organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  13. customrecrystallized (hexane/diethyl ether)

Sources & evidence

ORD record
ord-1fb2829ec95b4319b7a3f0a8ab53ac75
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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