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

HRID 1015361노트

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HRID 1015361 반응식
[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]

참가 물질

5

반응물 3

HCID 24386Thionyl Chloride2회HCID 178501163HCID 178501163, 화합물HCID 178505644HCID 178505644, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-19f03e7275e0498db1458668a65250ab
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07985755B2

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