Water → 6-Chloro-1-(4-fluoro-2-hydroxyphenyl)-1-hexanone

HRID 1368897Notes

Reaction equation

HRID 1368897 reaction equation
B(F)(F)F.[F:5][C:6]1[CH:7]=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=1.[Cl:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19](Cl)=[O:20].O>C(OCC)C>[Cl:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([C:9]1[CH:10]=[CH:11][C:6]([F:5])=[CH:7][C:8]=1[OH:12])=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 6356Boron trifluorideHCID 97433-FluorophenolHCID 880146-Chlorohexanoyl chloride

Product 1

HCID 185181746-Chloro-1-(4-fluoro-2-hydroxyphenyl)-1-hexanoneYield 85.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

Reaction under N2 atmosphere. BF3 in diethylether (215 ml) was cooled to 0° C. 3-Fluoro-phenol (0.25 mol) was added. 6-Chloro-hexanoyl chloride (0.51 mol) added and the resulting reaction mixture was stirred for 15 min at 0° C., then allowed to warm to room temperature. The reaction mixture was then stirred overnight at 130° C. The mixture was cooled room temperature. Water was added while cooling. This mixture was extracted twice with diisopropyl ether. The separated organic layer was dried, filtered and the solvent evaporated. The residue was by column chromatography over silica gel (eluent: CH2Cl2/hexane 50/50), then by HPLC (eluent: CH2Cl2/hexane 50/50). The fractions were collected and the solvent was evaporated, yielding 52.2 g of 6-chloro-1-(4-fluoro-2-hydroxyphenyl)-1-hexanone (interm 17).

Workup

  1. customReaction under N2 atmosphere
  2. customthe resulting reaction mixture
  3. temperatureto warm to room temperature
  4. stirringThe reaction mixture was then stirred overnight at 130° C
  5. temperatureThe mixture was cooled room temperature
  6. temperaturewhile cooling
  7. extractionThis mixture was extracted twice with diisopropyl ether
  8. customThe separated organic layer was dried
  9. filtrationfiltered
  10. customthe solvent evaporated
  11. customThe fractions were collected
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-a5d7ebb2432c40288729aef95769b997
Source dataset
uspto-grants-2003_06
Patent number
US06576640B1

Reaction notes

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