Ethylene Glycol → 1,3-Dioxolane, 2-[3-fluoro-4-(phenylmethoxy)phenyl]-2-methyl-

HRID 218035Notes

Reaction equation

HRID 218035 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[CH:11][C:10]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19](O)[CH2:20][OH:21].CC1C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([CH3:16])[O:21][CH2:20][CH2:19][O:17]2)=[CH:11][C:10]=1[F:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 27832201-[4-(Benzyloxy)-3-fluorophenyl]ethan-1-one

Product 1

HCID 598235101,3-Dioxolane, 2-[3-fluoro-4-(phenylmethoxy)phenyl]-2-methyl-

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1-(4-(benzyloxy)-3-fluorophenyl)ethanone 22 (23.8 g, 97.5 mmol), ethylene glycol (16.4 mL, 293 mmol), p-TsOH (930 mg, 4.88 mmol) and toluene (400 mL) was stirred under reflux conditions for 4 days, azeotropically removing water with a Dean-Stark trap. The mixture was cooled to room temperature and quenched by addition of saturated sodium bicarbonate solution (200 mL). The aqueous phase was back-extracted with toluene (3×200 mL). The combined organic phases were washed with brine (200 mL), dried over sodium sulfate, filtered and the solvent removed under reduced pressure to give 28.7 g (103%) of crude 23 as a yellow solid. Crude 23 was used without further purification. 1H NMR (CDCl3) δ: 7.39 (m, 5H), 7.22 (dd, 1H), 7.16 (dd, 1H), 6.95 (t, 1H), 5.12 (s, 2H), 4.12 (dd, 2H), 3.77 (dd, 2H), 1.62 (s, 3H). LCMS m/z=289.1 (M+H).

Workup

  1. customquenched by addition of saturated sodium bicarbonate solution (200 mL)
  2. extractionThe aqueous phase was back-extracted with toluene (3×200 mL)
  3. washThe combined organic phases were washed with brine (200 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-25ce0bce4d04473b997f737edff8a417
Source dataset
uspto-grants-2012_06
Patent number
US08198305B2

Reaction notes

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