HCID 86689435, compound → HCID 86689434, compound

HRID 1474495Notes

Reaction equation

HRID 1474495 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:17]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)=[CH:20][CH:19]=3)[C:16](=[O:31])[C:15]3[C:10](=[CH:11][C:12]([O:32][CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][O:34]4)=[CH:13][CH:14]=3)[O:9]2)=[CH:4][CH:3]=1.[CH3:39][Mg]Cl>C1COCC1>[I:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:17]([C:18]3[CH:19]=[CH:20][C:21]([O:24][CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)=[CH:22][CH:23]=3)[C:16]([CH3:39])([OH:31])[C:15]3[C:10](=[CH:11][C:12]([O:32][CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][O:34]4)=[CH:13][CH:14]=3)[O:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 86689435HCID 86689435, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 86689434HCID 86689434, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 90.0% 2-(4-iodophenyl)-7-((tetrahydro-2H-pyran-2-yl)oxy)-3-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)chroman-4-one (104.891 g, 150.7 mmol, 1.0 equiv.) in THF (1.2 L) at 5° C., was added Methylmagnesium chloride 3.0 M solution in THF (160.000 ml, 480.0 mmol, 3.2 equiv.) by addition funnel over 30 minutes. The temperature did not rise about 8° C. during the addition. The reaction was removed from the ice bath and stirred at room temperature and stirred for another hour. TLC (20% ethyl acetate in hexanes) showed the reaction had no starting material. The solution was cooled in an ice bath, and carefully quenched with saturated ammonium chloride (35 mL). Ethyl acetate (1.2 L) and water (1.2 L) were added to the reaction mixture, and the layers were separated. The aqueous layer was extracted with EA (1 L). The combined organic layer was washed with brine (1 L), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to yield a pale yellow foam (111.26 g crude). This material was used without further purification.

Workup

  1. additionby addition funnel over 30 minutes
  2. additionThe temperature did not rise about 8° C. during the addition
  3. customThe reaction was removed from the ice bath
  4. stirringstirred for another hour
  5. temperatureThe solution was cooled in an ice bath
  6. customcarefully quenched with saturated ammonium chloride (35 mL)
  7. additionEthyl acetate (1.2 L) and water (1.2 L) were added to the reaction mixture
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with EA (1 L)
  10. washThe combined organic layer was washed with brine (1 L)
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto yield a pale yellow foam (111.26 g crude)
  15. customThis material was used without further purification

Sources & evidence

ORD record
ord-c5dfe5cec87748838f2f0520998e8bf3
Source dataset
uspto-grants-2015_04
Patent number
US09018244B2

Reaction notes

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