Iodine → 3-(1,3-Dioxolan-2-yl)-1-(4-fluoro-3-methylphenyl)propan-1-ol

HRID 1643275Notes

Reaction equation

HRID 1643275 reaction equation
II.Br[CH2:4][CH2:5][CH:6]1[O:10][CH2:9][CH2:8][O:7]1.[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][C:13]=1[CH3:20]>C1COCC1>[O:7]1[CH2:8][CH2:9][O:10][CH:6]1[CH2:5][CH2:4][CH:16]([C:15]1[CH:18]=[CH:19][C:12]([F:11])=[C:13]([CH3:20])[CH:14]=1)[OH:17]

Participants

5

Reactant 3

HCID 807IodineHCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 27348744-Fluoro-3-methylbenzaldehyde

Product 1

HCID 595688013-(1,3-Dioxolan-2-yl)-1-(4-fluoro-3-methylphenyl)propan-1-olYield 33.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
63 °C

Procedure

To a suspension of Mg turnings (1.1 g, 0.05 g-at.) and catalytic amount of iodine in 200 mL THF was added dropwise 2-(2-bromoethyl)-[1,3]dioxolane (4.3 g, 0.02 mol) with heating over a period of 30 min. The resulting mixture was stirred for 30 min at 63° C. and then cooled to −30° C. and 4-fluoro-3-methyl-benzaldehyde (3.0 g, 0.02 mol) added slowly as a solution in 50 mL of THF. The temperature was maintained at −30° C. for 1 h and then slowly raised to room temperature over a period of 3 h. The excess Grignard was destroyed by the careful addition of 200 mL saturated aqueous NH4Cl. The mixture was extracted with ethyl acetate (3×100 mL) and the combined organic layers washed with brine (2×50 mL) and dried over Na2SO4. After evaporation of the solvent, the product was isolated by flash column chromatography eluting with 0% to 50% ethyl acetate/hexanes to give 1.6 g of the title compounds as a light yellow oil.

Workup

  1. temperaturewith heating over a period of 30 min
  2. temperaturecooled to −30° C.
  3. temperatureThe temperature was maintained at −30° C. for 1 h
  4. temperatureslowly raised to room temperature over a period of 3 h
  5. customThe excess Grignard was destroyed by the careful addition of 200 mL saturated aqueous NH4Cl
  6. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
  7. washthe combined organic layers washed with brine (2×50 mL)
  8. dry with materialdried over Na2SO4
  9. customAfter evaporation of the solvent
  10. customthe product was isolated by flash column chromatography
  11. washeluting with 0% to 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-c1ebbdb6ecf14c95904a40b6c640fd6a
Source dataset
uspto-grants-2012_02
Patent number
US08119692B2

Reaction notes

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