4-Chlorophenol → HCID 68998471, compound

HRID 2103326Notes

Reaction equation

HRID 2103326 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:20][CH2:19][C@@H:18]([O:21][C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=2)[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu](I)I.Cl.CN(C)CC(O)=O.O1CCOCC1>[C:9]([O:13][C:14]([N:16]1[CH2:20][CH2:19][C@@H:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([O:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[CH:24][CH:23]=2)[CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 3

HCID 46844-ChlorophenolHCID 10796Cesium carbonateHCID 68999936HCID 68999936, compound

Product 1

HCID 68998471HCID 68998471, compoundYield 99.8%

Reagents, catalysts & solvents 3

HCID 75605N,N-Dimethylglycine hydrochlorideCatalystHCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-chlorophenol (495 mg, 3.85 mmol), the product from step 1 (1 g, 2.57 mmol), cesium carbonate (1.67 g, 5.14 mmol), copper iodide (51 mg, 0.27 mmol), and N,N-dimethylglycine HCl (35 mg, 0.249 mmol), were taken into anhydrous dioxane (12 mL) in a nitrogen flushed 20 mL vial. The reaction was heated to 90° C. for 24 h. The mixture was concentrated to dryness, and the resulting oil was partitioned between water and ethyl acetate. The aqueous layer was washed with ethyl acetate 3×. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to dryness. The compound was purified by flash column chromatography (20:1 silica ratio, eluted with 20% ethyl acetate in hexane) to obtain the title product (1 g, ˜90%).;LCMS; m/z 390 (M) 88% pure; 1H NMR (400 MHz, DMSO); δ 1.41 (s, 9H), 2.00-2.20 (m, 2H), 3.32-3.60 (m, 4H), 4.98 (s, 1H), 6.76 (d, 2H, J=8.8,), 6.94-7.03 (m, 4H), 7.19 (d, 2H), J=8.8,), 9.70 (s, 1H).

Workup

  1. customflushed 20 mL vial
  2. concentrationThe mixture was concentrated to dryness
  3. customthe resulting oil was partitioned between water and ethyl acetate
  4. washThe aqueous layer was washed with ethyl acetate 3×
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness
  8. customThe compound was purified by flash column chromatography (20:1 silica ratio, eluted with 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ef7c7258505449bd86abd0a03a9fb930
Source dataset
uspto-grants-2009_08
Patent number
US07576102B2

Reaction notes

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