Thionyl Chloride → 4-(2-Fluorobenzoyl)cyclohexanecarboxylic Acid Methyl Ester

HRID 1015361Notes

Reaction equation

HRID 1015361 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]([OH:13])=O)[CH2:7][CH2:6]1)([O:3][CH3:4])=[O:2].S(Cl)(Cl)=O.[I-].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[Zn+]>O1CCCC1>[CH3:4][O:3][C:1]([CH:5]1[CH2:6][CH2:7][CH:8]([C:11](=[O:13])[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[F:19])[CH2:9][CH2:10]1)=[O:2]

Participants

5

Reactant 3

HCID 24386Thionyl Chloride2×HCID 178501163HCID 178501163, compoundHCID 178505644HCID 178505644, compound

Product 1

HCID 575168734-(2-Fluorobenzoyl)cyclohexanecarboxylic Acid Methyl EsterYield 67.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In an oven dried 1 neck round bottom flask with reflux condenser and stirbar, trans-4-carbomethoxycyclohexane-1-carboxylic acid (840 mg; 4.5 mmol) was heated to reflux in the presence of 15 mL thionyl chloride. After 3 hours reflux, mixture cooled to 40° C. under nitrogen flow, and excess thionyl chloride was removed at reduced pressure. Residue was taken up in 5 mL of dry tetrahydrofuran and added to a 0° C. mixture of 2-fluorophenylzinc iodide (9.0 mL; 4.5 mmol), tetrakis(triphenylphospine)palladium (0) (272 mg; 0.2 mmol) in 10 mL anhydrous tetrahydrofuran. Mixture was allowed to warm to room temperature over 16 hours. Reaction was quenched with 6 mL 1N HCl and ethyl acetate was taken in. Organics separated and aqueous re-extracted with 20 mL ethyl acetate. Combined organics were washed with sat. NaHCO3, water, brine and dried over MgSO4. Material was purified via flash silica plug (10:1) using 15% ethyl acetate in hexanes isocratic to give 800 mg of title compound. (67% yield)

Workup

  1. customIn an oven dried 1 neck round bottom flask
  2. temperaturewith reflux condenser
  3. temperatureAfter 3 hours reflux
  4. customwas removed at reduced pressure
  5. additionadded to a 0° C.
  6. customReaction
  7. customwas quenched with 6 mL 1N HCl and ethyl acetate
  8. customOrganics separated
  9. extractionaqueous re-extracted with 20 mL ethyl acetate
  10. washCombined organics were washed with sat. NaHCO3, water, brine
  11. dry with materialdried over MgSO4
  12. customMaterial was purified via flash silica plug (10:1)

Sources & evidence

ORD record
ord-19f03e7275e0498db1458668a65250ab
Source dataset
uspto-grants-2011_07
Patent number
US07985755B2

Reaction notes

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