2,4,6-Trimethylbenzeneacetyl chloride → 1-Methoxy-4-[2-(2,4,6-trimethyl-phenyl)-acetoxy]-piperidine-4-carboxylic acid ethyl ester

HRID 2035303Notes

Reaction equation

HRID 2035303 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([OH:14])[CH2:11][CH2:10][N:9]([O:12][CH3:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2].CN(C)C1C=CN=CC=1.CN(C1C=CN=CC=1)C.[CH3:33][C:34]1[CH:39]=[C:38]([CH3:40])[CH:37]=[C:36]([CH3:41])[C:35]=1[CH2:42][C:43](Cl)=[O:44]>N1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1([O:14][C:43](=[O:44])[CH2:42][C:35]2[C:34]([CH3:33])=[CH:39][C:38]([CH3:40])=[CH:37][C:36]=2[CH3:41])[CH2:7][CH2:8][N:9]([O:12][CH3:13])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 110307542,4,6-Trimethylbenzeneacetyl chlorideHCID 23202903HCID 23202903, compoundHCID 595847504-Hydroxy-1-methoxy-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 595847341-Methoxy-4-[2-(2,4,6-trimethyl-phenyl)-acetoxy]-piperidine-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-hydroxy-1-methoxy-piperidine-4-carboxylic acid ethyl ester (0.5 g, 2.46 mmol) in 15 ml pyridine under argon was added 4-dimethylaminopyridine DMAP (0.11 g, 0.9 mmol). The solution was cooled down to 0° C., then (2,4,6-trimethylphenyl)-acetyl chloride (0.58 g, 2.95 mmol) was added dropwise. The reaction mixture was warmed up to room temperature and left stirring for 3 days. Then the reaction mixture was concentrated and cold (0° C.) water was added. The aqueous phase was thoroughly extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography on silica gel (ethyl acetate/cyclohexane 1:4) to give pure 1-methoxy-4-[2-(2,4,6-trimethyl-phenyl)-acetoxy]-piperidine-4-carboxylic acid ethyl ester (compound P3.6) as light yellow oil. Yield: 610 mg.

Workup

  1. temperatureThe reaction mixture was warmed up to room temperature
  2. waitleft
  3. concentrationThen the reaction mixture was concentrated
  4. additioncold (0° C.) water was added
  5. extractionThe aqueous phase was thoroughly extracted three times with dichloromethane
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography on silica gel (ethyl acetate/cyclohexane 1:4)

Sources & evidence

ORD record
ord-062974ee7630408ea981c01a1d8dfedd
Source dataset
uspto-grants-2013_11
Patent number
US08574607B2

Reaction notes

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