Sodium Chloride → HCID 69524632, compound

HRID 854902Notes

Reaction equation

HRID 854902 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:21])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2.C([O-])([O-])=O.[K+].[K+].[CH:28]1(I)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[Na+].[Cl-]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([O:21][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 12289Iodocyclohexane2×HCID 69517568HCID 69517568, compound

Product 1

HCID 69524632HCID 69524632, compoundYield 3.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl 8-chloro-6-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 17a, Step 3 (1.00 g, 3.10 mmole) in anhydrous DMF (10.0 mL) was added KI (51.5 mg, (0.310 mmole), K2CO3 (1.29 g, 9.30 mmole) and cyclohexyl iodide (1.20 mL, 9.30 mmole). The suspension was heated at 50° C. for 17 h and then the temperature was slowly raised to 80° C. and stirred overnight. Additional cyclohexyl iodide (1.20 mL, 9.30 mmole) was added and the temperature was maintained at 100-120° C. for 3 days. The mixture was then cooled and poured into H2O (200 mL), which was saturated with solid NaCl. Following extraction with EtOAc (2×100 mL), the combined extracts were washed with brine (3×100 mL) and concentrated in vacuo. Purification by silica chromatography (6:1 hexanes:EtOAc) gave 45 mg (3.5% yield) of the product: EIHRMS m/z 404.0999 (M+, C19H20ClF3O4, Calc'd 404.1002).

Workup

  1. temperaturethe temperature was slowly raised to 80° C.
  2. temperaturethe temperature was maintained at 100-120° C. for 3 days
  3. temperatureThe mixture was then cooled
  4. extractionextraction with EtOAc (2×100 mL)
  5. washthe combined extracts were washed with brine (3×100 mL)
  6. concentrationconcentrated in vacuo
  7. customPurification by silica chromatography (6:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-38f18665704744cfab2c33b1f19a996f
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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