Iodine → HCID 67327154, compound

HRID 1023331Notes

Reaction equation

HRID 1023331 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)=[C:4]([F:13])[CH:3]=1.II.[CH2:16]1O[CH2:17]1.[NH4+].[Cl-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[F:40][C:41]([F:50])([F:49])[C:42]1[CH:43]=[CH:44][C:45]([OH:48])=[CH:46][CH:47]=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[F:13][C:4]1[CH:3]=[C:2]([CH2:16][CH2:17][O:48][C:45]2[CH:44]=[CH:43][C:42]([C:41]([F:49])([F:50])[F:40])=[CH:47][CH:46]=2)[CH:7]=[CH:6][C:5]=1[CH:8]1[O:12][CH2:11][CH2:10][O:9]1

Participants

9

Reactant 7

HCID 807IodineHCID 6354Ethylene Oxide2×HCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 678744-(Trifluoromethyl)phenolHCID 5462977Diethyl azodicarboxylateHCID 219386012-(4-Bromo-2-Fluorophenyl)-1,3-Dioxolane

Product 1

HCID 67327154HCID 67327154, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a THF (40 mL) solution of 2-(4-bromo-2-fluorophenyl)-1,3-dioxolane (3.29 g) was added Mg (406 mg) and I2 (135 mg), then the resultant mixture was refluxed for 5 hours. After cooling to 0° C., the reaction mixture was added ethylene oxide (12.5 mL, 1.1 M in THF), then the resultant mixture was stirred at 50° C. for 3 hours. The reaction mixture was added ethylene oxide (12.5 mL, 1.1 M in THF), the resultant mixture was stirred at 50° C. over night. The mixture was poured into saturated aqueous NH4Cl, and extracted with AcOEt. The organic layer was washed with water and saturated aqueous NaCl, dried over anhydrous Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=99/1 to 4/1) to afford a colorless oil. To a THF (10 mL) solution of that colorless oil and PPh3 (857 mg) and alpha,alpha,alpha-trifluoro-p-cresol (530 mg) were added DEAD (1.486 mL, 2.2 M in toluene) at 0° C., then the resultant mixture was stirred at room temperature over night. The reaction mixture was evaporated, to the residue was added n-hexane/AcOEt (4/1), then the mixture was filtered, and the filtrate was evaporated. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/0 to 9/1) to afford 2-(2-fluoro-4-{2-[4-(trifluoromethyl)phenoxy]ethyl}phenyl)-1,3-dioxolane as a colorless oil (0.552 g).

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with water and saturated aqueous NaCl
  3. dry with materialdried over anhydrous Na2SO4
  4. customevaporated
  5. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=99/1 to 4/1)
  6. customto afford a colorless oil
  7. customThe reaction mixture was evaporated, to the residue
  8. additionwas added n-hexane/AcOEt (4/1)
  9. filtrationthe mixture was filtered
  10. customthe filtrate was evaporated
  11. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/0 to 9/1)

Sources & evidence

ORD record
ord-6e31e2a60f1d499eac0334c72e8898aa
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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