Water → HCID 68654303, compound

HRID 1716101Notes

Reaction equation

HRID 1716101 reaction equation
[C:1]1(=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)=O)=[C:12]([F:25])[CH:11]=1.O.C([O-])([O-])=O.[K+].[K+]>O1CCCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16](=[C:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)=[C:12]([F:25])[CH:11]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10400CycloheptanoneHCID 11430Potassium CarbonateHCID 53661303HCID 53661303, compound

Product 1

HCID 68654303HCID 68654303, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of Zn powder (3.4 g, 51.5 mmol) in dry tetrahydrofuran (50 mL) was slowly added TiCl4 (2.7 mL, 25.1 mmol) at RT under a nitrogen atmosphere. The reaction mixture was heated at reflux for 2.5 h. To the reaction mixture was added a solution of cycloheptanone (2.4 mL, 20.3 mmol) and (4-bromo-2-fluoro-phenyl)-(4-hydroxy-phenyl)-methanone (76) (2 g, 6.78 mmol) in dry tetrahydrofuran (50 mL). The reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature, then water (40 mL) was added followed by 10% K2CO3 (40 mL). The reaction mixture was filtered through a pad of Celite and the pad was washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was loaded onto silica gel and purified by flash chromatography with a hexanes:EtOAc gradient (100:0 to 90:10) to give 2.24 g (88%) of compound 175. 1H NMR indicates that the product contains ˜3% cycloheptanone. 1H NMR (400 MHz, DMSO-d6): δ 1.43-1.50 (m, 8H), 2.05-2.08 (m, 2H), 2.23-2.24 (m, 2H), 6.65 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 7.14, (t, J=8.1 Hz, 1H), 7.32-7.35 (m, 1H), 7.44-7.47 (m, 1H), 9.33 (s, 1H).

Workup

  1. customat RT
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 2.5 h
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux for 2 h
  6. filtrationThe reaction mixture was filtered through a pad of Celite
  7. washthe pad was washed with EtOAc
  8. customThe filtrate was transferred to a separatory funnel
  9. customthe layers were separated
  10. extractionThe aqueous layer was extracted with EtOAc
  11. washthe combined organic layers were washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. custompurified by flash chromatography with a hexanes

Sources & evidence

ORD record
ord-89c285cb75424de3b9c2769cd6c72a88
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Reaction notes

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