Pyridine → Benzyl 4-acetylpiperidine-1-carboxylate

HRID 1424321Notes

Reaction equation

HRID 1424321 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20]C1(C)OC(=O)CC(=O)O1.N1C=CC=CC=1>C(Cl)Cl.O=S(Cl)Cl.CS(C)=O.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17](=[O:19])[CH3:20])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 1049PyridineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic Acid

Product 1

HCID 19065050Benzyl 4-acetylpiperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolventHCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Procedure

5.0 g (19.0 mmol) piperidine-1,4-dicarboxylic acid monobenzyl ester were dissolved in 200 ml DCM and 4.16 ml SOCl2. After heating 2 h to reflux the volatile components were removed under reduced pressure. The residue was dissolved in 200 ml DCM and 3.29 g (22.8 mmol) 2,2-dimethyl-[1,3]dioxane-4,6-dione as well as 4.6 ml (57 mmol) pyridine were added. The reaction mixture was stirred at room temperature over night, washed twice with 1 N aqueous HCl and brine, dried over Na2SO4 and concentrated under reduced pressure to be subsequently submitted to column chromatography on silica gel with n-hexane/ethyl acetate to yield a product, which was dissolved in 50 ml DMSO/water (95:5) and heated to 70° C. for 3 h. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed twice with 0.1 N aqueous HCl, saturated aqueous Na2CO3 and brine, dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using n-hexane/ethyl acetate as eluents to yield ketone (21).

Workup

  1. temperatureAfter heating 2 h
  2. temperatureto reflux the volatile components
  3. customwere removed under reduced pressure
  4. dissolutionThe residue was dissolved in 200 ml DCM
  5. washwashed twice with 1 N aqueous HCl and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto yield a product, which
  9. temperatureheated to 70° C. for 3 h
  10. customThe solvent was removed under reduced pressure
  11. dissolutionthe residue was dissolved in ethyl acetate
  12. washwashed twice with 0.1 N aqueous HCl, saturated aqueous Na2CO3 and brine
  13. dry with materialdried over Na2SO4
  14. customevaporated under reduced pressure
  15. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-70f396e96ecc47dcbf039641c85a0758
Source dataset
uspto-grants-2015_01
Patent number
US08927534B2

Reaction notes

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