Lithium Hydroxide → HCID 66777647, compound

HRID 2091196Notes

Reaction equation

HRID 2091196 reaction equation
Br[C:2]1[C:6]2[CH:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH:13]([NH:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=1)[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.[CH3:31][N:32](C)C=O.[OH-].[Li+]>O1CCCC1.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[C:31]([C:2]1[C:6]2[CH:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH:13]([NH:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)#[N:32]

Participants

9

Reactant 3

HCID 3939Lithium Hydroxide2×HCID 6228DimethylformamideHCID 66778141HCID 66778141, compound

Product 1

HCID 66777647HCID 66777647, compoundYield 94%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of methyl 4-{[(3-bromo-5-methoxy-1-benzofuran-2-yl)(cyclohexyl)methyl]amino}benzoate (1.46 g) synthesized above, zinc cyanide (362 mg) and N,N-dimethylformamide (30 mL) was added tetrakis(triphenylphosphine)palladium (0) (357 mg), and after deaeration, the mixture was stirred under argon atmosphere at 80° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (40% ethyl acetate/hexane) to give a yellow solid. To a solution (10 mL) of the obtained solid in tetrahydrofuran was added 1N lithium hydroxide aqueous solution (2.88 mL), and the mixture was stirred overnight with heating under reflux. Ethanol (10 mL) and water (10 mL) were added to the reaction mixture, and the mixture was stirred with heating under reflux for 3 hr. 1N lithium hydroxide aqueous solution (1.44 mL) was additionally added, and the mixture was stirred overnight with heating under reflux, and concentrated under reduced pressure. The residue was dissolved in water (20 mL), and 1N hydrochloric acid (4.35 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (547 mg, 94%) as a pale-yellow solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (40% ethyl acetate/hexane)
  6. customto give a yellow solid
  7. stirringthe mixture was stirred overnight
  8. temperaturewith heating
  9. temperatureunder reflux
  10. stirringthe mixture was stirred
  11. temperaturewith heating
  12. temperatureunder reflux for 3 hr
  13. stirringthe mixture was stirred overnight
  14. temperaturewith heating
  15. temperatureunder reflux
  16. concentrationconcentrated under reduced pressure
  17. dissolutionThe residue was dissolved in water (20 mL)
  18. addition1N hydrochloric acid (4.35 mL) was added at 0° C
  19. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-15d37cdf3f42460e98b7dfc2c5e254e4
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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