Hydrochloric Acid → HCID 135489364, compound

HRID 747876Notes

Reaction equation

HRID 747876 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13](I)=[CH:12][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([Mg]Br)(C)C.C([Si](C)(C)[C:27]1[CH:36]=[C:35]2[C:30]([C:31]([CH3:44])=[C:32]([C:38]3[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=3)[CH:33](O)[O:34]2)=[CH:29][CH:28]=1)(C)(C)C.Cl.[O:48]1CCCC1>CO>[CH3:44][C:31]1[C:30]2[C:35](=[CH:36][C:27]([OH:48])=[CH:28][CH:29]=2)[O:34][CH:33]([C:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:11][CH:12]=2)[C:32]=1[C:38]1[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran3×HCID 154806551-[2-(4-Iodophenoxy)ethyl]piperidineHCID 59750614HCID 59750614, compoundHCID 178418365HCID 178418365, compound

Product 1

HCID 135489364HCID 135489364, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-[2-(piperidin-1-yl)-ethoxy]-iodobenzene (2.56 g, 7.73 mmol, 3 eq), in tetrahydrofuran (10 mL) under argon at −78° C. was added dropwise isopropylmagnesium bromide (3.6 mL of 2.13 M, 7.73 mmol, 3 eq). The reaction mixture was then stirred for 2 hours at about −78° C. A tetrahydrofuran solution of 7-(tert-butyl-dimethyl-silanyl)-4-methyl-3-pyridin-4-yl-2H-chromen-2-ol (950 mg, 2.58 mmol, 1 eq, in 5 mL), prepared as in Example 27, was then added, the cooling bath was removed and the reaction mixture was allowed to warm to room temperature overnight. After about 18 hours, the reaction was worked-up with addition of saturated ammonium acetate solution (15 mL) and extraction with ethyl ether (2×). The combined organic extracts were washed with brine and water, dried with anhydrous sodium sulphate, filtered and evaporated to yield a sticky semisolid residue. To this solid in THF at room temperature was added 0.5 mL HCl in MeOH. The mixture was stirred for 30 min and quenched with sat. NaHCO3, partitioned between CH2Cl2 and water. The aqueous layer was extracted 3× with CH2Cl2. The combined organic phase was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to afford the crude material. The title product was isolated as a viscous, colorless, semisolid foam via chromatography on silica gel eluted with 3% methanol/dichloromethane.

Workup

  1. additionwas then added
  2. customthe cooling bath was removed
  3. temperatureto warm to room temperature overnight
  4. waitAfter about 18 hours
  5. additionthe reaction was worked-up with addition of saturated ammonium acetate solution (15 mL) and extraction with ethyl ether (2×)
  6. washThe combined organic extracts were washed with brine and water
  7. dry with materialdried with anhydrous sodium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a sticky semisolid residue
  11. stirringThe mixture was stirred for 30 min
  12. customquenched with sat. NaHCO3
  13. custompartitioned between CH2Cl2 and water
  14. extractionThe aqueous layer was extracted 3× with CH2Cl2
  15. washThe combined organic phase was washed with brine
  16. dry with materialdried over anhydrous Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customto afford the crude material

Sources & evidence

ORD record
ord-41f404d9725949578716246b75c02f29
Source dataset
uspto-grants-2008_07
Patent number
US07399767B2

Reaction notes

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