Iodine → 1-[(2-Fluorophenyl)methyl]cycloheptan-1-ol

HRID 1731818Notes

Reaction equation

HRID 1731818 reaction equation
[Mg].[F:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5]Cl.II.[C:13]1(=[O:20])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[Cl-].[NH4+]>C(OCC)C>[F:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][C:13]1([OH:20])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 5

HCID 807IodineHCID 9580Benzene, 1-(chloromethyl)-2-fluoro-HCID 10400CycloheptanoneHCID 25517Ammonium ChlorideHCID 5462224Magnesium

Product 1

HCID 137329251-[(2-Fluorophenyl)methyl]cycloheptan-1-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
30 °C

Procedure

To a suspension of 16.05 g of magnesium turnings in 200 ml of anhydrous diethyl ether was added a solution of 71.34 ml of o-fluorobenzyl chloride in 250 ml of ether at a rate sufficient to maintain the pot temperature at about 30° C. while cooling the flask in an ice water bath. The reaction was initiated by addition of a few iodine crystals. After the completion of the addition the mixture was stirred under nitrogen at ambient temperature for 45 minutes, and thereafter a solution of 58.9 ml of cycloheptanone in 200 ml of ether was added over a 25 minute period, keeping the pot temperature at about 20° C. with cooling. After the addition the mixture was stirred at ambient temperature for 1 hour and thereafter cooled to 8° C. and treated with 500 ml of saturated ammonium chloride solution (cautiously at first). After 10 minutes of vigorous stirring, the mixture was poured into a separatory funnel, the phases were separated and the aqueous phase was extracted with ether (2×250 ml). The combined ether extracts were washed with 250 ml of saturated ammonium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo to an oil weighing 109.94 g which crystallized to a solid (mp 35°-40° C.) after removal from high vacuum. A 10 g portion of this material was purified by preparative high performance liquid chromatography (HPLC hereafter) preparative using dichloromethane as a solvent; m.p. 35°-38° C.

Workup

  1. temperaturewhile cooling the flask in an ice water bath
  2. additionAfter the completion of the addition the mixture
  3. customat about 20° C.
  4. temperaturewith cooling
  5. additionAfter the addition the mixture
  6. stirringwas stirred at ambient temperature for 1 hour
  7. temperaturecooled to 8° C.
  8. waitAfter 10 minutes of vigorous stirring
  9. additionthe mixture was poured into a separatory funnel
  10. customthe phases were separated
  11. extractionthe aqueous phase was extracted with ether (2×250 ml)
  12. washThe combined ether extracts were washed with 250 ml of saturated ammonium chloride solution
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo to an oil
  16. customcrystallized to a solid (mp 35°-40° C.)
  17. customafter removal from high vacuum
  18. customA 10 g portion of this material was purified by preparative high performance liquid chromatography (HPLC hereafter)

Sources & evidence

ORD record
ord-4063e78d30b44080a9f6df6fd192642b
Source dataset
uspto-grants-1986_11
Patent number
US04623657

Reaction notes

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