Piperidine → HCID 1530257, compound

HRID 1993974Notes

Reaction equation

HRID 1993974 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:11])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 98372-(4-Fluorophenyl)acetic acidHCID 24386Thionyl Chloride

Product 1

HCID 1530257HCID 1530257, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

4-Fluorophenylacetic acid (280 g, 1.82 mol) was suspended in 1.9 L toluene followed by the careful addition of 185 mL thionyl chloride (303 g, 2.545 mol). The reaction was heated to 105° C. for 16 hr (overnight). The reaction was allowed to cool to room temperature and the volatiles were removed in vacuo. The crude acid chloride was dissolved in 1.9 L THF, cooled to 0° C., and 0.72 L piperidine (618 g, 7.27 mol) was added. The reaction vessel was allowed to warm to ambient temperature for 18 hr. The mixture was quenched with a saturated solution of aq. NaHCO3 and extracted several times with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, and filtered on a fritted funnel. The volatiles were removed in vacuo and the crude residue was purified on silica gel and eluted with a mixture of EtOAc/heptanes (0-75% gradient elution). This furnished the title compound. 1H-NMR (CDCl3): δ 1.32-1.42 (m, 2H), 1.48-1.64 (m, 4H), 3.34-3.42 (m, 2H), 3.54-3.60 (m, 2H), 3.69 (s, 2H), 6.90-7.05 (m, 2H), 7.18-7.24 (m, 2H) ppm.

Workup

  1. temperatureto cool to room temperature
  2. customthe volatiles were removed in vacuo
  3. dissolutionThe crude acid chloride was dissolved in 1.9 L THF
  4. temperaturecooled to 0° C.
  5. temperatureto warm to ambient temperature for 18 hr
  6. customThe mixture was quenched with a saturated solution of aq. NaHCO3
  7. extractionextracted several times with EtOAc
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered on a fritted funnel
  11. customThe volatiles were removed in vacuo
  12. customthe crude residue was purified on silica gel
  13. washeluted with a mixture of EtOAc/heptanes (0-75% gradient elution)

Sources & evidence

ORD record
ord-bd8ec255d45344f6a8ea2d3dcbe4c734
Source dataset
uspto-grants-2010_01
Patent number
US07652058B2

Reaction notes

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