3,3-Dimethylbutanoyl chloride → 1-(3,3-Dimethyl-butyryl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester

HRID 2193999Notes

Reaction equation

HRID 2193999 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH2:12][CH2:13][O:14][CH3:15])[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].[C:16]([CH2:20][C:21](Cl)=[O:22])([CH3:19])([CH3:18])[CH3:17]>C(N(CC)CC)C>[CH2:1]([O:3][C:4]([C:6]1([CH2:12][CH2:13][O:14][CH3:15])[CH2:7][CH2:8][N:9]([C:21](=[O:22])[CH2:20][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 815143,3-Dimethylbutanoyl chlorideHCID 567539694-(2-Methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 667874921-(3,3-Dimethyl-butyryl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl esterYield 48.9%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a solution of 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (0.646 g) under an argon atmosphere were added triethylamine (0.668 g, 0.92 ml) and tert-butyl acetyl chloride (0.44 g, 0.45 ml) under ice cooling. The reaction mixture was stirred at RT for 3 h. It was then partitioned between methylene chloride and aqueous 1M HCl, the layers were separated and the aqueous layer washed with 2M aqueous KHCO3 and dried over Na2SO4. The solvent was evaporated off, the residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 50%) to give 1-(3,3-Dimethyl-butyryl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester, (0.46 g) as a light yellow solid. MS (ESI): 314 (MH+).

Workup

  1. customIt was then partitioned between methylene chloride and aqueous 1M HCl
  2. customthe layers were separated
  3. washthe aqueous layer washed with 2M aqueous KHCO3
  4. dry with materialdried over Na2SO4
  5. customThe solvent was evaporated off
  6. customthe residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 50%)

Sources & evidence

ORD record
ord-cb871b72c8544bbdb27df37e65b010f5
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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