Hydrochloric Acid → HCID 66848046, compound

HRID 475432Notes

Reaction equation

HRID 475432 reaction equation
[Br:1][C:2]1[CH:33]=[CH:32][C:5]2[C:6]([C:9]3[CH:31]=[CH:30][CH:29]=[CH:28][C:10]=3/[CH:11]=[N:12]/C(C3C=CC(F)=CC=3)C3C=CC(F)=CC=3)=[N:7][O:8][C:4]=2[CH:3]=1.CC(C)([O-])C.[K+].I[CH2:41][CH:42]1[CH2:44][CH2:43]1.Cl>O1CCCC1.CC(C)=O>[Br:1][C:2]1[CH:33]=[CH:32][C:5]2[C:6]([C:9]3[CH:31]=[CH:30][CH:29]=[CH:28][C:10]=3[CH:11]([NH2:12])[CH2:41][CH:42]3[CH2:44][CH2:43]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2763048(Iodomethyl)cyclopropaneHCID 23665647Potassium tert-butoxideHCID 178505794HCID 178505794, compound2×

Product 1

HCID 66848046HCID 66848046, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine (Compound 8) (1.34 g) in dry tetrahydrofuran (15 mL) under nitrogen was cooled to −78° C. with stirring and a 1M solution of potassium tert-butoxide in tetrahydrofuran (3.2 mL) added dropwise. Solution turned dark purple. After 20 min (iodomethyl)cyclopropane (1.45 g) was added in one portion and solution slowly warmed to room temperature, stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate and evaporated to leave a dark red gum that was dissolved in acetone (20 mL) and an aqueous 2N HCl solution (15 mL) added and the mixture stirred overnight. The acetone was removed by evaporation and the aqueous solution extracted with dichloromethane. The aqueous solution was made basic with sodium bicarbonate and extracted with dichloromethane, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. SCX purification (eluting with methanol then ammonia in methanol) followed by flash chromatography on silica eluting with 0 to 5% methanol in dichloromethane gave the title product (0.39 g).

Workup

  1. stirringstirred at this temperature for 1.5 h
  2. customthen quenched by the addition of water (10 mL)
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. customevaporated
  7. customto leave a dark red gum that
  8. stirringthe mixture stirred overnight
  9. customThe acetone was removed by evaporation
  10. extractionthe aqueous solution extracted with dichloromethane
  11. extractionextracted with dichloromethane
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customevaporated under reduced pressure
  14. customSCX purification (
  15. washeluting with methanol

Sources & evidence

ORD record
ord-52a7c6034f6f4755be6692ee126e69a9
Source dataset
uspto-grants-2014_01
Patent number
US08637551B2

Reaction notes

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