HCID 10834141, compound → HCID 10155221, compound

HRID 275487Notes

Reaction equation

HRID 275487 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2([CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)=O)[CH2:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1>C1COCC1.[Ti](Cl)(Cl)(Cl)Cl.[Zn]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][C:10]3([CH2:14][C:15]=2[C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)[CH2:13][CH2:12][CH2:11]3)=[CH:4][CH:3]=1

Participants

5

Reactant 1

HCID 10834141HCID 10834141, compound

Product 1

HCID 10155221HCID 10155221, compoundYield 76.4%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen, 16.3 mL (149 mmol) of titanium(IV) chloride was slowly added to a suspension of 19.5 g (298 mmol) of zinc dust in 500 mL of anhydrous THF at -78° C. The resulting mixture was allowed to warm to ambient temperature and then to stir at reflux for 45 minutes. The reaction was cooled to ambient temperature prior to the addition of 19.27 g (49.6 mmol) of neat 1-(4-fluorophenyl)-2-[1-[2-[4-(methysulfonyl)phenyl]-2-oxoethyl]cyclobutan-1-yl]ethan-1-one (prepared in Step 6) by syringe. The reaction was allowed to stir at ambient temperature overnight, filtered through celite, and concentrated in vacuo. The residue was partitioned between ethyl acetate and water; the ethyl acetate phase was washed with brine, dried (MgSO4), and concentrated in vacuo. Purification by silica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane (20:80) gave 13.5 g (76%) of 6-(4-fluorophenyl)-7-[4-(methylsulfonyl)phenyl]spiro[ 3.4]oct-6-ene as a colorless solid: mp 123-124° C.; NMR (CDCl3) δ 1.85-1.98 (m, 2H), 2.08 (t, J=7 Hz, 4H), 2.98 (s, 4H), 3.04 (s, 3H), 6.92 (t, J=9 Hz, 7.05-7.13 (m, 2H), 7.30 (t, J=8HZ, 2H), 7.75 (t, J=8 Hz, 2H). MS (FAB) m/e 357 (M+H). Anal. Calc'd for C21H21FO2S: C, 70.76; H, 5.94; F, 5.53; S, 8.99. Found: C, 70.76; H, 6.10; F, 5.20; S, 8.96.

Workup

  1. temperatureat reflux for 45 minutes
  2. temperatureThe reaction was cooled to ambient temperature
  3. stirringto stir at ambient temperature overnight
  4. filtrationfiltered through celite
  5. concentrationconcentrated in vacuo
  6. customThe residue was partitioned between ethyl acetate and water
  7. washthe ethyl acetate phase was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane (20:80)

Sources & evidence

ORD record
ord-27ee421922a247439f4fdc0975a426a2
Source dataset
uspto-grants-1995_02
Patent number
US05393790

Reaction notes

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