3-Chlorobenzoic Acid → 5-(4-Fluorophenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hepta-4,6-diene

HRID 1379722Notes

Reaction equation

HRID 1379722 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][C:10]3([CH2:13][C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[CH2:12][CH2:11]3)=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=O.ClC1C=C(C=CC=1)C(O)=O.C([O-])(=O)C.[Na+]>ClCCl.C(O)(=O)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]([C:15]3[CH:16]=[CH:17][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:19][CH:20]=3)=[CH:13][C:10]3([CH2:11][CH2:12]3)[CH:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 4473-Chlorobenzoic AcidHCID 70297m-Chloroperbenzoic acidHCID 517045Sodium AcetateHCID 98517705-(4-Fluorophenyl)-6-(4-methylsulfonylphenyl)spiro[2.4]hept-5-ene

Product 1

HCID 99279125-(4-Fluorophenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hepta-4,6-dieneYield 64%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 500 mg (1.46 mmol) of 5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hept-5-ene (from Step 11) in 7 mL of dichloromethane was treated with 480 mg (55% peroxyacid, 1.53 mmol) of m-chloroperoxybenzoic acid (MCPBA). The reaction was stirred at ambient temperature for 2.5 hours, washed with aqueous saturated sodium bisulfite, dried (MgSO4), and concentrated in vacuo to give a mixture of desired expoxide intermediate and m-chlorobenzoic acid; this crude mixture in 10 mL of acetic acid and 1 mL of water was subsequently treated with 500 mg (6.1 mmol) of sodium acetate and stirred at 80° C. for 10 hours. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was partitioned between water and ethyl acetate; the organic phase was washed with aqueous saturated sodiun bicarbonate, water, brine, dried (MgSO4), and reconcentrated in vacuo. Purification by silica gel chromatography gave 317 mg (64%) of 5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hepta-4,6-diene as a colorless solid: mp 119°-128° C. (dec); NMR (CDCl3) δ 1.81 (s, 4H), 3.06 (s, 3H), 6.22 (d, J=2 Hz, 1H), 6.36 d, J=2 Hz, 1H), 6.95 (5, J=8 Hz, 2H), 7.02-7.18 (m, 2H), 7.33 (d, J=8 Hz, 2H), 7.80 (d, J=8 Hz, 2H). MS (FAB) m/e (rel intensity) 347 (100) (M+Li). HRMS. Calc'd for C20H17FO2S: 340.0933. Found: 340.0952. Anal. Calc'd for C20H17FO2S: C, 69.29; H, 4.97; F, 5.45. Found: C, 69.21; H, 5.23; F, 5.81.

Workup

  1. washwashed with aqueous saturated sodium bisulfite
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give
  5. stirringstirred at 80° C. for 10 hours
  6. temperatureThe reaction mixture was cooled to ambient temperature
  7. concentrationconcentrated in vacuo
  8. customThe residue was partitioned between water and ethyl acetate
  9. washthe organic phase was washed with aqueous saturated sodiun bicarbonate, water, brine
  10. dry with materialdried (MgSO4)
  11. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-3e07720b19e34a058c2fabd9cc7ec4b1
Source dataset
uspto-grants-1997_09
Patent number
US05672627

Reaction notes

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