Hydrochloric Acid → 8-fluoro-3-(4-fluorophenyl)-2,3-dihydro-4H-1-benzothiopyran-4-one

HRID 22194Notes

Reaction equation

HRID 22194 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:12][S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[Cl-].[Cl-].[Cl-].[Al+3].Cl>S(Cl)(Cl)=O>[F:20][C:15]1[C:14]2[S:13][CH2:12][CH:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:9](=[O:11])[C:19]=2[CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6451240Aluminum(III) ChlorideHCID 199275564-Fluoro-alpha-[[(2-fluorophenyl)thio]methyl]benzeneacetic acid

Product 1

HCID 197367508-fluoro-3-(4-fluorophenyl)-2,3-dihydro-4H-1-benzothiopyran-4-oneYield 82%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent2×

Conditions

Temperature
0 °C

Procedure

The acid from Step C (4.5 g, 15 mmole) was dissolved in 30 ml of thionyl chloride and refluxed for four hours. After cooling the thionyl chloride was concentrated and the residue taken up in carbon tetrachloride. The carbon tetrachloride was concentrated and the residue was taken up in 30 ml of dichloroethane. To the dichloroethane solution being cooled in an ice bath, was added aluminum trichloride (total of 2.1 g, 16 mmole) in three portions every 15 min. After stirring the black solution for an additional 30 min at 0° C., a 5% aqueous HCl solution was added. The aqueous phase was separated and extracted twice with methylene chloride. The organic phases were combined, dried (MgSO4), and concentrated to give the crude product as a yellow oil (3.4 g, 82% yield). 1H NMR (CDCl3) δ: 7.97 (1H, dd, J=3, 9 Hz), 7.19 (6H, m), 4.12 (1H, dd, J=4, 12 Hz), 3.58 (1H, m), 3.32 (1H, ddm J=4, 12 Hz).

Workup

  1. temperaturerefluxed for four hours
  2. concentrationwas concentrated
  3. concentrationThe carbon tetrachloride was concentrated
  4. temperatureTo the dichloroethane solution being cooled in an ice bath
  5. customThe aqueous phase was separated
  6. extractionextracted twice with methylene chloride
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-cf484d06a6464aae8cc12143c37092fb
Source dataset
uspto-grants-1995_06
Patent number
US05428027

Reaction notes

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